cell and tissue research volume 348 issue 2 2012 [doi 10.1007%2fs00441-012-1398-4] gaetano thiene,...

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REVIEW

Why and how to support screening strategies to prevent

sudden death in athletes

Gaetano Thiene & Domenico Corrado & Ilaria Rigato &

Cristina Basso

Received: 2 March 2012 /Accepted: 5 March 2012 /Published online: 29 March 2012# Springer-Verlag 2012

Abstract Sudden death in athletes occurs because of the

existence of hidden cardiovascular disorders which, duringeffort, may jeopardize the electrical stability of the heart,

triggering ventricular tachycardia and/or fibrillation. Apart

from rare conditions of ion channel diseases in the setting of

a structurally normal heart, in which the disorder may be

easily diagnosed on basal or stress test ECG, cardiac abnor-

malities at risk of causing sudden death may affect the aorta

(Marfan syndrome), the coronary arteries (congenital coro-

nary artery anomalies, premature coronary atherosclerosis),

the myocardium (hypertrophic and arrhythmogenic cardio-

myopathy), the valves (bicuspid aortic valve, mitral valve

prolapse) and the conduction system (pre-excitation syn-

dromes). These structural heart disorders may be detected

by ECG and/or echo. The employment of these tools at pre-

partic ipa tio n screen ing can help to identi fy concea led

anomalies, which may play a major role in early diagnosis,

risk stratification, and prevention of sudden death.

Keywords Athlete . Sudden death . Pathology . Screening .

Prevention

Young athletes’ death has raised a debate in the U.S. and

critics say that a wider screening including ECG could

detect several hidden heart defects and save lives.There is a rationale for supporting such a screening

strategy. The following statement may be convincing.

1) Sport activity is healthy and should be recommended,

particularly in the young. However, there is a paradox

in the exercise that is like a two-edged sword: it can

simultaneously offer protection for the risk of suddendeath in those who are regularly engaged and can

increase a short-term risk of sudden death due to

underlying heart disease.

2) Although rare, the risk of sudden death does exist

during sport activity (Corrado et al. 1990). The recent

report in the media of the video-recorded collapse and

death of a first-ranking athlete like Puerta, soccer

player in Sevilla, who was found at postmortem to

be affected by arrhythmogenic cardiomyopathy, repre-

sented a dramatic event. In the Veneto Region Pro-

spective Research Project of sudden death in the

young, the incidence of the phenomenon in athletes

was calculated as 2.3/100,000/year, nearly 3-fold the

incidence of 0.9/100,000/year in non-athletes (Corrado

et al. 2003).

3) The higher incidence of sudden death in athletes vs

non-athletes gives evidence that effort may be the

trigger for life-threatening arrhythmias. This does not

mean that “ per se” sudden death is due to effort; on the

contrary, it is related to the existence of concealed

cardiovascular abnormalities, either structural or func-

tional, which act as predisposing factors to cardiac

arrest. Both autonomic imbalance and vigorous cardio-

vascular performance act as triggers during exercise.

The concealed defect affects the major components of

the heart: aorta, coronary arteries, myocardium, valves,

conduction system, ion channels (Corrado et al. 2005a ).

4) The paradox is that a heart with subtle morbid entities

can exhibit optimal, even extreme myocardial contrac-

tion activity and cardiac output with excellent physical

performance. Conditions with cardiac failure or overt

ischemic heart disease (i.e., dilated cardiomyopathy,

obstructive coronary artery disease with previous

G. Thiene (*) : D. Corrado : I. Rigato : C. Basso

University of Padua Medical School,

Padua, Italy

e-mail: [email protected]

Cell Tissue Res (2012) 348:315 – 318

DOI 10.1007/s00441-012-1398-4



myocardial infection) present with dyspnea, fatigue, or

angina in such a way as to limit exercise. It is the

abrupt onset of electrical instability with ventricular

fibrillation (“heart delirium”), not preceded by any

previous symptoms, which is life-threatening (Thiene

et al. 2010).

5) In the majority of cases these abnormalities are sus-

pected or even diagnosed at basal 12-lead ECG (seecardiomyopathy, ion channel disease, av block, preexci-

tation syndrome, etc.). The ECG is the easy way to

identify subjects at risk and may be considered a life-

saving tool (Corrado et al. 2008). Of course, there may

be alarming symptoms (syncope, palpitations, dizziness)

that should not be overlooked. This is the reason why

an ECG should be included in routine pre-participation

screening of young athletes for eligibility or disqualifi-

cation. Among 33,735 athletes examined in the Veneto

Region, according to the Italian screening program, 22

(0.07%) turned out to be affected by hypertrophic car-

diomyopathy: 18 (82%) had abnormal ECG, whereas

only five (23%) had a positive family history or cardiac

murmur at the physical examination, with nearly60% less sensibility (Corrado et al. 1998). The supe-

riority of the Italian program (including ECG)

(Decree of the Italian Ministry of Health 1982) vs

the American program (without ECG) (Maron et al.

2007) is clear-cut. In arrhythmogenic cardiomyo-

pathy, ECG abnormalities may even be superior to

Fig. 1 International Society of Sports Cardiology flowchart

316 Cell Tissue Res (2012) 348:315 – 318



imaging techniques in detecting minor forms of the

disease with discrete fibro-fatty infiltration of the free

wall, in the absence of dyskinesia/aneurysms and

with preserved ejection fraction of the right ventricle

(Pelliccia et al. 2008).

6) Implementation in Italy of a preparticipation screening

program for sport eligibility since 1982 (Decree of

the Italian Ministry of Health 1982), which includesECG, resulted in 90% decrease of sudden death in

athletes, aged 20 – 35 years, in the Veneto Region in

the time interval 1980 – 2004 (Corrado et al. 2006).

This was mostly due to the ECG detection of cardio-

myopathies thanks to dissemination of diagnostic

criteria and awareness of the existence of these harm-

ful morbid entities by sport physicians and cardiolo-

gists. Sudden death due to cardiomyopathy dropped

from 1.5/100,000/year in the pre-screening era to 0.15/

100,000/year of the late screening period (Corrado et

al. 2006). Nowadays, dangerous morbid entities such

as arrhythmogenic and hypertrophic cardiomyopathyshould no longer escape detection during the visit at

pre-participation screening. It is time to turn the page

in the approach to pre-participation screening for com-

petitive sport activity by introducing not only physical

but also instrumental examination worldwide, with

ECG playing a pivotal role. Screening young athletes

with 12-lead ECG in addition to cardiovascular family

history and physical examination has been proven to be

cost-effective (Corrado & McKenna 2007).

7) There are potentially dangerous abnormalities such as

valve disease (mitral valve prolapse, bicuspid aortic

valve) that may be ECG-silent, thus escaping detec-

tion if only ECG is employed. In this setting, cardiacmurmur due to mild regurgitation should raise suspi-

cion, justifying the recommendation of echocardiogra-

phy as a diagnostic tool. Half of the young people

affected by bicuspid aortic valve present increased

diameter of the aortic root, even in the absence of

any murmur. Whether 2D echocardiography should

be used as a routine tool for screening, in addition to

ECG, should be taken into serious account, consider-

ing that most of those at risk present gross structural

deformities of the heart.

8) The existence of a link between ischemic heart disease

and lifestyle risk factors (smoke, obesity, drug abuselike cocaine) should suggest blood lipid assessment and

in selected cases even CT coronary angiography as com-

plementary investigations. Bear in mind that exercise

adds a 2.6-fold risk of sudden death to young people

affected by concealed atherosclerotic coronary artery

Fig. 2 Different approaches to

prevention

Cell Tissue Res (2012) 348:315 – 318 317



disease and a 79.0-fold risk if affected by congenital

coronary artery anomalies (Corrado et al. 2003). The

sensitivity of ECG, both basal and stress test, in dis-

covering concealed coronary artery disease is poor,

both for acquired (coronary atherosclerosis) and con-

genital anomalies. This represents a major limitation

and indeed sudden deaths still occurring in the athletes

of our Region are mostly due to undetected coronaryartery disease.

9) Up to 30 – 40% of sudden cardiac death in athletes are

ascribable to heredo-familiar disorders, with or with-

out structural abnormalities. Molecular mutation anal-

ysis as well as cardiological and genetic screening in

first-degree family members should be carried out to

reveal healthy carriers at potential risk and may be

life-saving (Basso et al. 2010).

10) Sports pre-participation screening, including genetic

screening when deemed necessary, aims not only

to detect and disqualify athletes at risk but also to

reassure the vast majority of healthy, unaffected people, who are then allowed to continue safely in the

pleasure of sports activity or profession (Corrado et al.

2005b).

A flow chart has been put forward by the International

Society of Sports Cardiology adopting the Italian protocol

of Cardiovascular Preparticipation Screening (Corrado et al.

2010) (Fig. 1).

Of course, physical examination, personal and family

history and 12-lead ECG represent a first-level investigation

to raise the suspicion of an underlying disorder. If positive, a

cascade of investigations then begins: second-level withnon-invasive tools (stress test, signal average ECG, echo,

cardiac magnetic resonance, coronary angio CT, genetic

analysis) and third-level with invasive tools (coronary

angiography, electrophysiological study, electroanatomic

mapping, endomyocardial biopsy), aimed at achieving a

definitive diagnosis.

The prevention of sudden death in the young and

athletes is nowadays feasible and can be accomplished

in different ways (Fig. 2): sport disqualification that acts

in removing exercise as a trigger, drug therapy or ablation

on arrhythmic mechanism and implantation of defibrillator

on cardiac arrest.All of these are palliative interventions, which do not

influence disease prevention and cure. This represents a

major challenge for basic science and translational cardio-

vascular medicine.

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