Screening professional athletes for cardiovascular diseases at risk of cardiac arrest

There was a moment of real panic during the Denmark’s opening Euro 2020 match with Finland, when the professional soccer player Christian Eriksen suddenly collapsed with the loss of consciousness due to a cardiac arrest (CA) (Figure 1A). The anxiety for the life of the athlete lasted a short time because he recovered his cardiovascular function a few minutes later, thanks to the efficacy of the manoeuvres of cardiopulmonary resuscitation including the use of the automated external defibrillator (AED) (Figure 1B). Although the identification of the cause of the CA is still under clinical investigation, the mechanism was clearly ‘arrhythmic’ in nature, i.e. an episode of ventricular tachycardia or ventricular fibrillation leading to the sudden interruption of cardiac pump with the block of circulation and cerebral perfusion. The miraculous resuscitation with the recovery of cardiac function and consciousness of the athlete was the result of early defibrillation of the potentially lethal arrhythmia that was triggered by sports activity and would have been fatal without the shock therapy delivered by the AED. The Denmark player Christian Eriksen collapsed on the pitch because of a cardiac arrest just before half-time in the Euro 2020 match between Denmark and Finland (A). Although his heart stopped working, thanks to life-saving cardiopulmonary resuscitation including external defibrillations he was awake when left the stadium (B). By courtesy of ilgazzettino.it. The Denmark player Christian Eriksen collapsed on the pitch because of a cardiac arrest just before half-time in the Euro 2020 match between Denmark and Finland (A). Although his heart stopped working, thanks to life-saving cardiopulmonary resuscitation including external defibrillations he was awake when left the stadium (B). By courtesy of ilgazzettino.it. This episode of aborted sudden death (SD) brings back the memory to the past tragic events of professional soccer players, such as Marc Vivian Foe, Antonio Puerta, and Pier Mario Morosini who experienced CA in the pitch, rapidly and inexorably evolving to death because of unsuccessful treatment. The story of Eriksen is emblematic of the extraordinary advances in the last years of the management of CA occurring during sports activity, mostly due to the availability of in-the-field AED. For this reason, we are really enthusiastic to entitle this CardioPulse piece ‘Screening professional athletes for cardiovascular diseases at risk of cardiac arrest’ (rather than sudden death): indeed, the increasingly consistent evidence that early electric shock is life-saving makes the use of the terms ‘cardiac arrest’ and ‘sudden death’ in the athlete fortunately no longer interchangeable, being CA a successfully treatable event.1 The Eriksen’s case has revived the interest of media and medical community on the reason why healthy professional athletes can unexpectedly experience CA during sports activity and what prevention strategy might have avoided such a dramatic event. Relevant questions are: may some causes of CA in top level athletes remain clinically concealed? and is cardiovascular screening before participation in sports of limited efficacy for identification of athletes with at-risk cardiovascular disorders? ‘Competitive athletes’ are individuals who are engaged in exercise training on a regular basis and participate in official sports competition; a subgroup is the ‘professional athletes’. Several studies demonstrated that atherosclerotic coronary artery disease is the most common condition responsible of CA/SD in middle-aged and senior athletes, while younger (<35 years) competitive athletes have a wide range of cardiovascular causes including congenital and inherited disorders.2 The most prevalent causes of CA in young competitive athletes are genetic heart muscle diseases, such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, followed by congenital anomalies of coronary arteries, aortic rupture in Marfan's syndrome, myocarditis (either acute myocardial inflammation or post-inflammatory myocardial scar), and valvular diseases, including aortic valve stenosis and mitral valve prolapse. A sizeable proportion of athletes experiencing CA/SD has no evidence of structural heart disease and the cause of their CA is related to primary electrical cardiac conditions, namely inherited cardiac ion-channel defects (channelopathies) including long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and Brugada syndrome. Preparticipation screening evaluation offers the potential to identify asymptomatic athletes who have potentially lethal cardiovascular abnormalities and, then, to protect them from the risk of sport-related CA/SD.3,4 The target athletic population and the screening protocol vary among European and extra-European countries. Screening by history and physical examination only, which is recommended in the USA, has limited sensitivity to identify athletes at risk because most individuals with undetected cardiovascular diseases are asymptomatic and CA/SD most often represent the first clinical manifestation. The long-running Italian experience showed that adding an ECG definitively improves the screening sensitivity and substantially reduces the risk of fatalities among competitive athletes.5,6 The screening protocol of Italian professional athletes, in addition to history, physical examination, and basal ECG, includes by law annual maximal exercise testing and biannual echocardiogram. Additional tests such as Holter monitoring, cardiac MRI, or coronary CT scan, are requested for selected athletes who had positive findings at the initial evaluation. Athletes diagnosed with clinically relevant cardiovascular diseases are managed according to currently available guidelines. Of note, in Italy, preparticipation screening is repeated on a regular basis every year in non-professional athletes and every 6 months in professional athletes. A time-trend analysis of the incidence of SD in young competitive athletes in the Veneto region of Italy over 26 years (1979–2004) showed a decline of mortality by 90% after the introduction of the nationwide screening program.7 Most importantly, the study demonstrated that the mortality reduction was a reflection of a lower incidence of SD from ECG detectable cardiomyopathies and channelopathies. Up to two-third of at-risk cardiovascular diseases are diagnosed by virtue of serial (annual) screening that intercepts genetic cardiomyopathies with a late-onset phenotypic expression or newly acquired heart muscle disease.8 It is noteworthy, however, that no screening strategy is able to identify all athletes at the risk of CA/SD (Figure 2). Acute myocarditis may occur unpredictably and some cardiac conditions such as atherosclerotic coronary artery disease and congenital anomalies of coronary arteries usually are asymptomatic and non-associated with abnormalities on basal 12-lead ECG.3–4 According to the ESC guidelines, asymptomatic middle-age/senior athletes, in whom the most common cause of SD is coronary artery disease, before engaging in a vigorous physical activity should be evaluated using the ESC risk score systems and then by exercise testing and/or coronary CT, which are reserved to those with a high or very high estimated cardiovascular risk.9 Efficacy of preparticipation screening, diagnostic tests, and prevalence of cardiovascular diseases at risk of cardiac arrest/sudden death in professional athletes. The dotted red arrow denotes the decreasing efficacy of preparticipation screening of professional athletes in relation to the increasing complexity of diagnostic tests required for identification of at-risk diseases. The routine screening protocol (medical history, physical examination, basal electrocardiogram, echocardiogram, and exercise testing) provides a good sensitivity for the identification of most prevalent conditions associated with the risk of cardiac arrest/sudden death in young professional athletes, such as cardiomyopathies, channelopathies, Wolff–Parkinson–White syndrome and mitral valve prolapse. The screening shows a lower diagnostic yield for less prevalent causes of cardiac arrest/sudden death, i.e. non-ischemic left ventricular scar, coronary artery disease, congenital coronary anomalies, acute myocarditis, and idiopathic ventricular fibrillation, whose detection needs advanced imaging examinations (cardiac magnetic resonance and coronary computed tomography angiography) or invasive tests (endomyocardial biopsy and electrophysiologic study). The importance of in-the-field automated external defibrillator increases for treating unexpected arrhythmic cardiac arrest due to cardiac diseases more difficult to identify by preparticipation screening. Generally, genetic characterization by molecular testing is indicated in the presence of a disease overt phenotype. AED, automated external defibrillator; Brugada, Brugada syndrome; CA, cardiac arrest; CAD, coronary artery disease; CCA, congenital coronary anomaly; CMR, cardiac magnetic resonance; CCTA, coronary computed tomography angiography; CPVT, catecholaminergic polymorphic ventricular tachycardia; ECG, electrocardiogram; ECHO, echocardiography; EMB, endomyocardial biopsy; EPS, electrophysiologic study; ET, exercise testing; HCM, hypertrophic cardiomyopathy; Hx&PE, medical history and physical examination; LQTS, long QT syndrome; MVP, mitral valve prolapse; NILVS, non-ischemic left ventricular scar; SD, sudden death; VF, ventricular fibrillation; WPW, Wolff–Parkinson–White syndrome. Efficacy of preparticipation screening, diagnostic tests, and prevalence of cardiovascular diseases at risk of cardiac arrest/sudden death in professional athletes. The dotted red arrow denotes the decreasing efficacy of preparticipation screening of professional athletes in relation to the increasing complexity of diagnostic tests required for identification of at-risk diseases. The routine screening protocol (medical history, physical examination, basal electrocardiogram, echocardiogram, and exercise testing) provides a good sensitivity for the identification of most prevalent conditions associated with the risk of cardiac arrest/sudden death in young professional athletes, such as cardiomyopathies, channelopathies, Wolff–Parkinson–White syndrome and mitral valve prolapse. The screening shows a lower diagnostic yield for less prevalent causes of cardiac arrest/sudden death, i.e. non-ischemic left ventricular scar, coronary artery disease, congenital coronary anomalies, acute myocarditis, and idiopathic ventricular fibrillation, whose detection needs advanced imaging examinations (cardiac magnetic resonance and coronary computed tomography angiography) or invasive tests (endomyocardial biopsy and electrophysiologic study). The importance of in-the-field automated external defibrillator increases for treating unexpected arrhythmic cardiac arrest due to cardiac diseases more difficult to identify by preparticipation screening. Generally, genetic characterization by molecular testing is indicated in the presence of a disease overt phenotype. AED, automated external defibrillator; Brugada, Brugada syndrome; CA, cardiac arrest; CAD, coronary artery disease; CCA, congenital coronary anomaly; CMR, cardiac magnetic resonance; CCTA, coronary computed tomography angiography; CPVT, catecholaminergic polymorphic ventricular tachycardia; ECG, electrocardiogram; ECHO, echocardiography; EMB, endomyocardial biopsy; EPS, electrophysiologic study; ET, exercise testing; HCM, hypertrophic cardiomyopathy; Hx&PE, medical history and physical examination; LQTS, long QT syndrome; MVP, mitral valve prolapse; NILVS, non-ischemic left ventricular scar; SD, sudden death; VF, ventricular fibrillation; WPW, Wolff–Parkinson–White syndrome. Recent clinical and pathological studies have demonstrated that a non-ischaemic left ventricular myocardial scar may be a not so uncommon and clinically concealed substrate of life-threatening arrhythmias in the athlete.10 This myocardial lesion may be caused by a variety of myocardial diseases, including myocarditis, sarcoidosis, and genetic cardiomyopathies. Although non-ischaemic left ventricular scar is a potential source of effort-induced ventricular arrhythmias detectable by exercise testing and/or Holter monitoring, the diagnostic power of standard ECG is limited because suspicious abnormalities such as low QRS voltages in limb leads and T-wave inversion in lateral leads are found in a minority of affected patients. Moreover, the segmental nature of the left ventricular myocardial scar involving the epicardial-midmyocardial wall layers, but sparing the subendocardium which most contributes to myocardial thickening, explains why it is usually missed by echocardiography and only evidenced as late gadolinium enhancement on cardiac magnetic resonance.10 The difficulty to identify affected athletes by routine preparticipation ECG screening makes this condition one of most challenging and unpredictable causes of CA/SD during sports, as shown by the fatal event of the Italian professional soccer player Pier Mario Morosini in 2012. To conclude, the best strategy to fight SD during sports is to synergistically combine primary prevention by preparticipation identification of athletes with at-risk cardiovascular diseases and secondary prevention by the availability of on-site AED which provides life-saving early defibrillation in case of unpredictable arrhythmic CA, like that experienced by Christian Eriksen. Conflict of interest: none declared.