Management of mature athletes with cardiovascular conditions

Andrew D’Silva MBBS, BSc (Hons), MRCP (UK), Sanjay Sharma, BSc (Hons),

MBChB, (Hons), MD, FRCP (UK), FESC

Clinical Cardiology and Academic Group

St George’s University of London

St George’s University Hospital Foundation NHS Trust

Address for correspondence

Sanjay Sharma

Professor of Cardiology

Cardiology Clinical & Academic Group

St George’s, University of London

Cranmer Terrace

London. SW17 ORE

E mail: sasharma@sgul.ac.uk

Words: 3672

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Management of mature athletes with cardiovascular conditions

Learning Objectives

To appreciate the benefits of exercise training and safety issues in exercise and

sport.

To recognize the risk factors and mechanisms of sudden cardiac death during

and after strenuous exercise with specific population challenges.

To understand the contraindications to exercise/sporting competition and the

recommendations for professional and recreational sport participation.

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Introduction

Exercise is a potent therapy for the prevention1-4 and rehabilitation5 of

cardiovascular disease, including the management of risk factors for

atherosclerotic cardiovascular disease6. It is important to recognize, however,

that an “exercise paradox” exists where vigorous physical activity transiently

elevates the risk of sudden cardiac death (SCD) (Figure 1). The risk is greatest in

individuals who are not accustomed to regular exercise and undertake high

intensity physical activity with little or no systematic training7-9.

In a previous review in the Journal, we outlined the management of young

competitive athletes with cardiovascular conditions10. This population has been

the main focus of attention for pre-participation screening11 12, as the early

detection of inherited cardiomyopathies and arrhythmic syndromes has the

potential to prevent decades of lost life. Though widely debated13, the methods of

screening in this population are generally acceptable and particularly, the

inclusion of an ECG is effective in detecting the majority of potentially fatal

cardiac conditions relevant to this population14 15.

Sudden cardiac deaths among young competitive athletes, however, account for

just over 6% of all exercise related SCDs16. A far greater burden falls to non-elite,

older athletes over 35 years of age, where the cause is overwhelmingly due to

coronary artery disease (CAD) attributing to over 80% of deaths17-19 (Figure 2).

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In this article, we define mature competitive athletes as individuals, above 35

years of age, who compete in events with an emphasis on excellence and

undertake regular systematic training. Notably, the population at risk is

predominantly composed of mature recreational athletes, who by comparison,

undertake a variety of informal recreational sports, which may be vigorous in

nature, though without stipulation on achieving excellence or undertaking

regular training. Evidence is sparse on this latter group, who require no

regulation or organizational affiliation and therefore provide little opportunity

for systematic examination through professional surveillance.

Whilst pre-participation screening in young competitive athletes is adopted by

many countries and international sporting organizations11 12 20, the

recommendations for mature athletes draw even greater controversy, not least

because of the lack of evidence demonstrating that ischaemic heart disease (IHD)

detection algorithms translate to a reduction in exercise-related SCD. As

increasing physical activity is heavily promoted in society for the substantial

health benefits and there is an increasing population of middle-aged individuals

who participate in mass endurance events, the issue is highly relevant and

deserving of attention. Many aspects of the previous review10, also hold

relevance to an older population of athletes. This article will focus specifically on

the cardiovascular conditions of greater relevance to mature athletes.

Hypertension

Hypertension is the most common cardiovascular condition in the general

population and affects almost a third of the population aged over 40 years. The

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precise prevalence of hypertension in mature athletes is unknown but may not

be too dissimilar compared with the general population. Influencing factors

include age, sex and sporting discipline and intensity of sport. Performance-

enhancing agents, such as anabolic steroids and frequent reliance on non-

steroidal anti-inflammatory agents, should also be considered as a potential

cause of hypertension in athletes.

Static (resistance or isometric) exercise is associated with elevations in blood

pressure, whereas predominantly dynamic forms of exercise are associated with

falls in blood pressure persisting for up to 24 hours after exercise. Athletes

achieving elevations of systolic blood pressure >200 mmHg may be predisposed

to hypertension despite normal blood pressure values at rest and should be

evaluated comprehensively with 24-hour ambulatory blood pressure

monitoring21.

Control of hypertension is of paramount importance in the prevention of IHD,

stroke and heart failure. Though hypertension is not implicated as a direct cause

of SCD in athletes, it is associated with an increased risk of complex ventricular

arrhythmias and therefore appropriate emphasis should be placed on the correct

diagnosis, assessment of target end organ damage and optimal blood pressure

(BP) control, using principles advocated in the general population with

hypertension23.

Sports may have an impact on the choice of antihypertensive agents. In

competitive athletes, beta-blockers and diuretics may be considered as doping

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agents for some sports, particularly those where an advantage can be gained

through weight loss or control of tremor24. In addition, neither agent is ideal for

endurance athletes, as beta-blockers frequently impair exercise performance and

diuretics may cause dangerous electrolyte and fluid disturbances. Calcium

channel blockers, ACE-inhibitors and angiotensin-II receptor blockers are better

choices for hypertensive endurance athletes24.

Arrhythmia

Bradyarrhythmias

Sinus bradycardia is common in the majority of well-trained athletes25 26, though

the exact underlying mechanism remains unclear. Classical theories implicate

enhancement of parasympathetic tone through increased vagal stimulation27.

Meanwhile, modern animal studies suggest that a reduction in the If (funny)

current could be responsible for bradycardia through intrinsic sinus node

changes, specifically, downregulating ion-channels associated with

potassium/sodium hyperpolarisation28-30.

First-degree atrioventricular (AV) block is a common training-related ECG

finding resulting from delayed conduction in the AV node14. Endurance athletes

also demonstrate a higher prevalence of type 1 second-degree AV block 31 32 and

periods of low atrial or junctional escape rhythms, at rates of 40 to 60 bpm, are

also normal phenomena. Occasionally, marked sinus bradycardia (< 40 bpm) at

rest or sinus pauses > 3 seconds can be found in asymptomatic, well-trained

endurance athletes33. Such findings are usually benign, more evident at rest,

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particularly during sleep and do not require intervention in asymptomatic

individuals.

These bradyarrhythmias are usually eliminated with exercise, providing a useful

diagnostic tool. The presence of symptoms such as lightheadedness, presyncope,

syncope or exertional fatigue may require long periods of ambulatory

monitoring for symptom-rhythm correlation and detection of pathology.

Higher degree AV blocks, including type 2 second-degree AV block (Mobitz type

II) and complete heart block, are very uncommon and require comprehensive

investigation for underlying pathology including structural heart disease,

infectious and infiltrative causes (particularly Lyme disease and sarcoidosis

respectively in those aged under 55 years)34 35. Pacemaker implantation is

indicated where the pathological substrate is not reversible. A diagnosis of

cardiac sarcoidosis requires consideration of SCD risk, including the decision to

implant a cardioverter-defibrillator (ICD)36. Cardiac magnetic resonance imaging

may provide valuable tissue characterization, with the detection of inflammation,

oedema and scar in addition to information provided by echocardiography. Care

must be taken not to mistake second degree 2:1 AV block with Wenckebach

physiology from true Mobitz type II AV block with 2:1 conduction37. This can

usually be achieved by exercise ECG testing though electrophysiological study

may be required in exceptional cases38.

Interventricular Conduction Delay Incomplete right bundle branch block (RBBB),

is common and does not require further investigation in asymptomatic athletes14.

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Complete RBBB is rarer occurring in up to 3% and may be associated with a non-

pathological increase in right ventricular chamber size39, resulting from athletic

training. International recommendations for ECG interpretation recognize

isolated RBBB as a potentially normal variant, though in some cases RBBB may

arise from pathological processes causing right ventricular pressure or volume

overload40.

Left bundle branch block (LBBB) is usually a marker of underlying cardiac

pathology. Detailed investigation is indicated for structural heart disease and

IHD. Syncope or presyncope, may be potentially attributable to higher degrees of

AV block, where ambulatory monitoring and electrophysiological study may be

useful. Athletes with abnormal AV conduction, characterized by a HV interval

>90 ms or a His-Purkinje block, should be considered for a cardiac pacemaker,

whereas those with structurally normal hearts and normal electrophysiological

study may participate in all competitive activities38. Asymptomatic rate-

dependent LBBB is frequently benign in the presence of a structurally normal

heart, however, its induction at low heart rates may be a subtle indicator of

disease and worthy of comprehensive evaluation38. A schema for evaluating

athletes with bradycardia and/or conduction delays is outlined in figure 3.

Athletes with Permanent Pacemakers and ICDs

Athletes with permanent pacemakers and ICDs may participate in sports where

the underlying heart condition does not preclude participation24 38. Athletes who

are pacing dependent and those with ICDs should avoid engaging in collision

sports and sports involving projectiles that can cause damage to the device. For

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athletes with pacemakers who are not pacing dependent, it is prudent to wear

protective equipment if engaging in contact sports although such practice is not

recommended38. Pacemaker programming should aim to ensure appropriate rate

adaptation during exercise and if persistent sinus rhythm is present, this may be

used for tracking. During follow up, exercise testing and 24h Holter monitoring

may assist in optimizing programming for improved pacing rate responsiveness

in some athletes. Athletes with ICDs may be considered for participation in

sports with higher peak static and dynamic components than class IA if free from

ventricular arrhythmia requiring device therapy for 3 months. Such athletes

require careful counseling regarding the potential risk of inappropriate shocks

and device-related trauma42.

Tachyarrhythmias

Endurance athletes experience a five-fold increased risk of atrial fibrillation

(AF)43. The total accumulated lifetime physical activity appears to be the critical

factor determining AF development. Most studies suggest that athletes

developing exercise-induced AF have been engaged in more than 10 years of

regular exercise training44-48. In one study > 2,000 hours of lifetime vigorous

exercise was associated with odds ratio of 4 for the presence of AF48. Another

study demonstrated that those who exercised more intensively and achieved

faster race times, were at higher risk of AF over a 9 year follow up period than

slower atheletes49. In the wider population, a U-shaped relationship is thought to

exist between physical activity and AF incidence48 50, where engagement in low to

moderate physical activity reduces the risk of AF from a sedentary baseline but

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increasing doses, to the levels and intensity described above, may elevate risk.

Presumably, modest physical activity is valuable in offsetting conventional risk

factors for AF such as hypertension, obesity and IHD, however, mechanisms

underpinning the development of exercise-induced AF in endurance athletes

remain incompletely understood. Atrial structural remodelling, resulting in

dilatation and fibrosis, has been proposed as a potential maladaptive response to

vigorous exercise contributing to AF development. Convincing arguments have

also been made for enhanced parasympathetic tone potentially being

responsible through shortening the atrial refractory period, facilitating re-entry

formation and subsequent establishment of AF51. In reality, the pathophysiology

of exercise-induced AF is likely to be multifactorial and may involve individual

susceptibility factors that are yet to be discovered52.

Mature recreational athletes who develop AF without a substantial background

of cumulative exercise should be evaluated for the conventional causes of atrial

fibrillation, such as hypertension, IHD, valvular heart disease, alcohol abuse and

thyrotoxicosis. The management of AF and ventricular arrhythmia were outlined

in detail in the previous review10.

Ischaemic Heart Disease

Atherosclerotic CAD is a potentially fatal condition facing athletes over 35 years

of age18. Sedentary individuals, however, who have the most to gain from regular

physical activity are paradoxically at greater risk of exercise-associated cardiac

arrest and myocardial infarction with vigorous exercise7 8 53. A striking 9:1 male

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predominance is seen in SCD among competitive athletes54 and this increases to

20:1 among individuals engaged in recreational exercise16, with large registries

reporting proportions of 93%55 - 95%16 of SCDs occurring in men. Potential

explanations for this sex discrepancy in SCDs include a relatively lower

participation rate and engagement at lower intensity levels among women

although hormonal influences cannot be disregarded.

The most common mode of SCD during sporting activity is an abrupt ventricular

tachyarrhythmia17. It is notable that many deaths in marathons occur in the final

quartile of the event54 56, suggesting that an electrolyte and/or metabolic

component may contribute to risk. Limited postmortem studies support acute

coronary plaque rupture pathology in sudden deaths occurring during emotional

stress or strenuous activity57. It is possible that demand ischaemia, variation in

sympathetic activity, vascular reactivity and increase in platelet aggregation

during exertion also play a role in precipitating acute coronary events and

ventricular arrhythmia.

Athletes with known CAD, having suffered an acute coronary syndrome (ACS) or

anginal chest pain are at increased risk of myocardial infarction (MI) associated

with vigorous physical exertion58. For this reason, current recommendations

from both the European Society of Cardiology (ESC)24 and the American Heart

Association/American College of Cardiology (AHA/ACC)59 advocate risk

stratification for recurrent events, inducible ischaemia and arrhythmia. A high

probability of exercise-induced cardiac events is indicated by the presence of any

of the following: symptoms of ischaemia, reduced exercise capacity, left

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ventricular ejection fraction < 50%, haemodynamically significant coronary

stenosis, exercise-induced ischaemia or complex ventricular tachyarrhythmia.

Athletes with any of these features should be advised to limit themselves to

sports with low dynamic and low to moderate static demands, once symptoms

have stabilized and at least 3 months after an acute MI or coronary

revascularization procedure.

Of paramount importance is compliance with optimized secondary prevention

medical therapy to treat underlying, established CAD and reduce the risk of

future events. Two particular medications are of worthy of mention as they can

result in a reduction in athletic performance. Beta-blockers confer significant

benefit in patients with reduced left ventricular ejection fraction post-ACS and

should be continued indefinitely at tolerated target doses despite adverse effects

on athletic performance. The issue is more contentious in patients with normal

left ventricular function. Though current recommendations advocate continued

treatment post-MI60-62, in asymptomatic, fully revascularized, low-risk patients,

strong arguments can be made to individualize treatment on the basis of

symptoms and tolerability63-65.

Effective statin therapy achieving targeted lipid lowering is critically important

in cardiovascular secondary prevention. Unfortunately, athletes and physically

active individuals experience myalgia more commonly with statins66 67. The

importance of lifelong compliance must be impressed upon the athlete, as return

to exercise is not an adequate substitute for evidence-based therapy.

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Athletes may have clinically concealed CAD, where they are asymptomatic

though demonstrate unequivocal ischaemia during provocative testing coupled

with angiographic evidence of haemodynamically significant coronary artery

stenosis. Such individuals should be risk stratified in same way as symptomatic

patients.

Finally, athletes with proven CAD who do not have haemodynamically significant

coronary stenosis (< 50% luminal narrowing), inducible ischaemia or complex

ventricular arrhythmias on provocative testing may undertake all competitive

activities, provided resting left ventricular ejection fraction is > 50% and there is

adherence to medical therapy59. These recommendations also apply to athletes

with coronary revascularization and are summarized in figure 4. The most recent

AHA/ACC recommendations adopt a much more liberal position to competitive

exercise with underlying CAD and depart significantly from previous consensus

documents, which confined them to competition in disciplines with low dynamic

and low/moderate static components under previous Bethesda US guidelines68.

The new leniency is despite CAD being responsible for 80% of SCDs in mature

athletes17 18 with no contemporary evidence to support the safety of sports

participation in this group. Communication with athletes with proven CAD

should include explanation of these uncertainties, including that CAD may

progress despite appropriate treatment, that acute cardiac events can occur at

sites of only mild coronary stenoses and that fatal arrhythmias may still arise

from demand ischaemia during exercise.

Prevention of Sudden Cardiac Death in Mature Athletes

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Given that the overwhelming majority of SCD affecting mature athletes are

attributable to CAD, recommendations regarding pre-participation evaluation of

mature athletes seem logical and prudent. Such recommendations have been

developed by the AHA72 and European Association of Cardiovascular Prevention

and Rehabilitation (EACPR)73. Unfortunately, neither approach has been tested

prospectively or shown to be effective in reducing exercise-related

cardiovascular events. Common elements to these recommendations include an

initial self-assessment questionnaire, aiming to identify known cardiovascular

disease, risk factors or symptoms. Following this, a physician’s detailed

cardiovascular evaluation is recommended for those with positive self-

assessment, aiming to highlight those who might benefit from maximal exercise

testing to detect underlying CAD.

The main differences provided by the EACPR recommendations are in

distinguishing whether an individual is sedentary or active before undertaking

an increase in physical activity and the level of intensity of the intended activity.

These additions recognize that both factors contribute to SCD risk7-9 16. Figure 5

summarizes the EACPR recommendations in two management algorithms74.

Given the size of the population concerned and the lack of resources to support

organized systematic screening programs for mature athletes, such a stratified

approach beginning with self-assessment allows a large proportion of healthy

individuals to be granted eligibility for sports participation without unnecessary

obstacles to increasing physical activity in the general population73. A physician-

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led cardiovascular evaluation includes history, physical examination, estimation

of 10-year cardiovascular risk using a validated scoring system75 76 and a resting

ECG.

The value of maximal exercise testing for asymptomatic athletes at high

cardiovascular risk in order to prevent SCD is more debatable. ECG exercise

testing has established prognostic value78-80, widespread availability and

relatively low cost. Inducible ischaemia and complex ventricular arrhythmias can

be assessed simultaneously in a maximally tolerated, graded manner providing

valuable additional information regarding exercise capacity and fitness. A

number of limitations to ECG exercise testing are worthy of mention. The

predictive value of ECG stress testing for exercise-related cardiovascular events

in asymptomatic, middle-aged men is low81, with 18% sensitivity and 92%

specificity78, largely owing to low disease prevalence in a relatively healthy

population. False-positive exercise tests are also a considerable problem,

particularly for older athletes82 and women83 84 and generate additional

diagnostic testing with associated cost and anxiety. Diagnostic ischaemic ECG

changes develop at an advanced stage of the ischaemia cascade and indicate the

presence of haemodynamically significant coronary stenosis. Plaque rupture

resulting in arrhythmic SCD, however, can occur in coronary lesions with only

mild to moderate stenosis85, escaping detection. Negative functional tests may

therefore be falsely reassuring and in some cases neither the treadmill nor

pharmacological stress agent in the imaging laboratory is able to adequately

reproduce the haemodyamic and metabolic stresses associated with athletic

competition and resultant demand ischaemia. Finally, endurance athletes tend to

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have supranormal coronary perfusion reserve;86 endurance training significantly

improves endothelial function87 and higher intensity exercise stimulates

coronary artery collateral growth88. These phenomena may account for atypical

presentations of CAD in endurance athletes, who may experience only

breathlessness or reduced exercise performance, rather than classical anginal

symptoms. In such cases, a negative exercise test is not reassuring and it is our

practice to proceed to CT coronary angiography, based on a wealth of anecdotal

experience of athletes with reduced performance and normal exercise tests but

with severe CAD at coronary angiography.

Future Directions in the Management of Mature Athletes

Given that vulnerable, mild to moderate coronary stenoses may be a substrate

for exercise-associated cardiac events, in the context of haemodynamic,

adrenergic and metabolic stress, this raises the possibility that coronary artery

calcium scoring (CACS) and/or computed tomography coronary angiography

(CTCA) may be effective screening tools in mature athletes. CACS and CTCA have

proven predictive value for MI and SCD over clinical risk stratification89 90. In a

recent study of 318 asymptomatic male athletes aged over 45 years, CT

identified occult CAD in 19%, where exercise ECG testing was negative during a

high work load91. Other studies suggest that CACS improves prediction of MI or

death due to CAD, only in intermediate risk patients (Framingham Risk Score 10-

20%)92 but adds no predictive power for those with low risk (Framingham Risk

Score <10%) as assessed by traditional cardiovascular disease risk factors92-94.

There are, in addition, implications of cost effectiveness, radiation exposure,

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potential contrast reactions and incidental findings associated with CACS/CTCA.

Moreover, studies in mature athletes suggest that endurance exercise may be

associated with a greater burden in coronary calcification91 95. Whether this

translates to hard clinical end points, such as ACS events or SCD, is yet to be

determined. Two recent publications suggest that plaque morphology in mature

athletes is more frequently of a stable, calcified type96 97. In contrast relatively

sedentary individuals with similarly low Framingham scores show a greater

proportions of mixed morphology and soft plaques which are more vulnerable to

rupture97.

A study of 102 male runners over 50 years of age, demonstrated a positive

association between higher coronary artery calcium scores and late Gadolinium

enhancement (LGE) on cardiac magnetic resonance imaging (MRI), which was

seen in 12%. Interestingly, the LGE distribution was consistent with myocardial

scarring resulting from IHD in only 42%. The majority demonstrated LGE in a

non-ischaemic, mid-myocardial, patchy distribution, raising the possibility that

these findings may arise through distinct underlying mechanisms. The

prevalence of LGE in athletes was not statistically different from that seen in

controls and therefore these findings should be interpreted with caution95.

The aforementioned studies, however, enrolled relatively small cohorts and are

therefore vulnerable to confounding factors and underpowered to address long-

term clinical outcomes. The studies also found that those athletes demonstrating

LGE, had greater accumulated years of exercise exposure99-101. Our own

experience suggests that focal fibrosis in the region of the right ventricular

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insertion points is present in over 40% of mature and younger endurance

athletes and may be adaptive rather than maladaptive. Large, prospective trials

in mature athletes, with long endurance exercise exposure, are required to

determine the cause and clinical significance of coronary calcification and

ventricular fibrosis identified in mature athletes.

Conclusion

Mature athletes commonly experience structural and electrical cardiac

remodelling consistent with the ‘athlete’s heart’.

Greater habitual physical activity is a public health imperative, crucial in curbing

rapidly growing epidemics, particularly type 2 diabetes and obesity. Vigorous

exercise, however, can also transiently elevate the acute risk of SCD in

predisposed individuals. IHD is responsible for the majority of deaths among

mature athletes and men possess a nine-fold greater risk than women. Detection

of underlying CAD in individuals who increase their physical activity level is

highly desirable as a potential strategy to reduce SCDs, however, effective pre-

participation screening protocols have not yet been proven in mature athletes.

Current recommendations advocate selective ECG stress testing, however this

approach and alternatives suffer important limitations. The evidence base for

mature athletes is sparse and research in this area to inform clinical practice is

desperately needed. Key priorities in future research should include evaluating

optimal strategies to reduce exercise-associated cardiac events in mature

athletes and to establish whether or not high volume accumulated exercise

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exposure has clinically important sequelae. Athletes with hypertension and

hypercholesterolemia may experience troublesome adverse effects on treatment

and therefore medications should be personalized depending on choices

available and according to patient risk/benefit profile.

Key messages

Exercise is overwhelmingly beneficial for cardiovascular health, though

vigorous intensity activity transiently elevates the risk of SCD for a small

number of individuals with underlying cardiac conditions.

Bradycardia and conduction blocks are common in athletes but high

degree AV blocks are associated with pathology and require intervention.

Atherosclerotic coronary artery disease is the principle cause of SCD in

the mature athlete and men are significantly more susceptible than

women.

Uncertainty remains over the best strategy to prevent SCD in mature

athletes and further research is needed.

The Corresponding Author has the right to grant on behalf of all authors and

does grant on behalf of all authors, an exclusive licence (or non exclusive for

government employees) on a worldwide basis to the BMJ Publishing Group Ltd

and its Licensees to permit this article (if accepted) to be published in HEART

editions and any other BMJPGL products to exploit all subsidiary rights.

Figure legends

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Figure 1. Exercise paradox.

SCD, sudden cardiac death.

Data taken from Nocon et al.1, Warburton et al.6, Marijon et al.17, Moore et al.2,

McTiernan et al.3, Hamer et al.4

Figure 2. Variation in sudden cardiac death incidence and causes across different

age groups.

RV, right ventricular; VT, ventricular tachycardia.

Reproduced with permission from La Gerche et al.19

Figure 3. Investigation of athletes with bradycardia and/or conduction delays.

AVB, atrioventricular block; CAD, coronary artery disease; cLBBB, complete left

bundle branch block; CMR, cardiac magnetic resonance scan; cRBBB, complete

right bundle branch block; ECG, electrocardiogram; EP, electrophysiological

study.

Figure 4. Diagnosis and management algorithm for athletes with cardiovascular

conditions including which patients benefit from referral to tertiary level

specialist centres.

ACE, angiotensin-converting enzyme; AV, atrioventricular; BP, blood pressure;

CAD, coronary artery disease; ECG, electrocardiogram; EP, electrophysiological

study; ICD, implantable cardioverter-defibrillator; LBBB, left bundle branch

block; MRI, magnetic resonance imaging; RBBB, right bundle branch block.

Reference to classes of sports, relating to dynamic and static components,

pertains to the Mitchell classification published in the previous review10

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Figure 5. European Association of Cardiovascular Prevention and Rehabilitation

pre-participation cardiovascular evaluation protocol for asymptomatic

sedentary adult/senior individuals (A) and active adult/senior individuals (B).

ECG, electrocardiogram; Hx, history; PA, physical activity; Phys.exam., physical

examination.

Reproduced with permission from Corrado et al.74

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