1D'Silva A, Sharma S. Heart 2017;0:1–10. doi:10.1136/heartjnl-2016-310744

IntroductIonExercise is a potent therapy for the prevention1–4 and rehabilitation5 of cardiovascular disease, including the management of risk factors for athero-sclerotic cardiovascular disease.6 It is important to recognise, 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 under-take high intensity physical activity with little or no systematic training.7–9

In a previous review in the journal, we outlined the management of young competitive athletes with cardiovascular conditions.10 This population has been the main focus of attention for preparticipa-tion screening,11 12 as the early detection of inher-ited cardiomyopathies and arrhythmic syndromes has the potential to prevent decades of lost life. Though widely debated,13 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 population.14 15

SCDs among young competitive athletes, however, account for just over 6% of all exercise-re-lated SCDs.16 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).

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 organisational affiliation and therefore provide little opportunity for systematic examination through professional surveillance.

While preparticipation screening in young competitive athletes is adopted by many countries and international sporting organisations,11 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.

HypertensIonHypertension is the most common cardiovascular condition in the general population and affects almost a third of the population aged over 40 years. The 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 associ-ated with elevations in blood pressure (BP), whereas predominantly dynamic forms of exercise are asso-ciated with falls in BP persisting for up to 24 hours after exercise. Athletes achieving elevations of systolic BP >200 mmHg may be predisposed to hypertension despite normal BP values at rest and should be evaluated comprehensively with 24-hour ambulatory BP monitoring.21

Control of hypertension is of paramount impor-tance 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 arrhyth-mias and therefore appropriate emphasis should be placed on the correct diagnosis, assessment of target end organ damage and optimal BP control, using principles advocated in the general population with hypertension.22

Management of mature athletes with cardiovascular conditionsAndrew D’Silva, Sanjay Sharma

education in Heart

to cite: D’Silva A, Sharma S. Heart Published Online First: [please include Day Month Year]. doi:10.1136/heartjnl-2016-310744

Clinical Cardiology and Academic Group, St George’s University of London, St George’s University Hospital Foundation NHS Trust, London, UK

correspondence toProfessor Sanjay Sharma, Cardiology Clinical & Academic Group, st George’s, University of London, Bloomsbury, London WC1E 7HU, UK; sasharma@ sgul. ac. uk

Learning objectives

► To appreciate the benefits of exercise training and safety issues in exercise and sport.

► To recognise 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.

Heart Online First, published on October 15, 2017 as 10.1136/heartjnl-2016-310744

Copyright Article author (or their employer) 2017. Produced by BMJ Publishing Group Ltd (& BCS) under licence.

2 D'Silva A, Sharma S. Heart 2017;0:1–10. doi:10.1136/heartjnl-2016-310744

education in Heart

Figure 1 Exercise paradox. AF, atrial fibrillation; 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 al3 and 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

Sports may have an impact on the choice of anti-hypertensive agents. In competitive athletes, beta-blockers and diuretics may be considered as doping agents for some sports, particularly those where an advantage can be gained through weight loss or control of tremor.23 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 inhib-itors and angiotensin II receptor blockers are better choices for hypertensive endurance athletes.23

3D'Silva A, Sharma S. Heart 2017;0:1–10. doi:10.1136/heartjnl-2016-310744

education in Heart

ArrHytHmIABradyarrhythmiasSinus bradycardia is common in the majority of well-trained athletes,24 25 though the exact under-lying mechanism remains unclear. Classical theories implicate enhancement of parasympathetic tone through increased vagal stimulation.26 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 hyperpolarisation.27–29

First-degree atrioventricular (AV) block is a common training-related ECG finding resulting from delayed conduction in the AV node.14 Endur-ance athletes also demonstrate a higher prevalence of type 1 second-degree AV block,30 31 and periods of low atrial or junctional escape rhythms, at rates of 40–60 bpm, are also normal phenomena. Occa-sionally, marked sinus bradycardia (<40 bpm) at rest or sinus pauses >3 s can be found in asymp-tomatic, well-trained endurance athletes.32 Such findings are usually benign, more evident at rest, particularly during sleep and do not require inter-vention in asymptomatic individuals.

These bradyarrhythmias are usually eliminated with exercise, providing a useful diagnostic tool. The presence of symptoms such as lightheaded-ness, 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 under-lying pathology including structural heart disease, infectious and infiltrative causes (particularly Lyme disease and sarcoidosis respectively in those aged under 55 years).33 34 Pacemaker implanta-tion is indicated where the pathological substrate is not reversible. A diagnosis of cardiac sarcoid-osis requires consideration of SCD risk, including the decision to implant a cardioverter defibrillator (ICD).35 Cardiac MRI may provide valuable tissue characterisation, with the detection of inflamma-tion, 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 conduction.36 This can usually be achieved by exercise ECG testing though electro-physiological study may be required in exceptional cases.37

Interventricular conduction delayIncomplete right bundle branch block (RBBB) is common and does not require further investiga-tion in asymptomatic athletes.14 Complete RBBB is rarer occurring in up to 3% and may be asso-ciated with a non-pathological increase in right ventricular chamber size,38 resulting from athletic training. International recommendations for ECG

interpretation recognise isolated RBBB as a poten-tially normal variant, though in some cases RBBB may arise from pathological processes causing right ventricular pressure or volume overload.39

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 electro-physiological study may be useful. Athletes with abnormal AV conduction, characterised by an 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 activities.37 Asymptomatic, rate-de-pendent LBBB is frequently benign in the presence of a structurally normal heart; however, its induc-tion at low heart rates may be a subtle indicator of disease and worthy of comprehensive evaluation.37 A schema for evaluating athletes with bradycardia and/or conduction delays is outlined in figure 3.

AtHLetes wItH permAnent pAcemAkers And IcdsAthletes with permanent pacemakers and ICDs may participate in sports where the underlying heart condition does not preclude participation.23 37 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 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 recommended.37 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 24-hour Holter monitoring may assist in optimising programming for improved pacing rate responsive-ness 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 counselling regarding the potential risk of inappro-priate shocks and device-related trauma.40

tAcHyArrHytHmIAsEndurance athletes experience a fivefold increased risk of atrial fibrillation (AF).41 The total accu-mulated 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 training.42–46 In one study >2000 hours of lifetime vigorous exer-cise was associated with an odds ratio of 4 for the presence of AF.46 Another study demonstrated that those who exercised more intensively and achieved faster race times were at higher risk of AF over a

4 D'Silva A, Sharma S. Heart 2017;0:1–10. doi:10.1136/heartjnl-2016-310744

education in Heart

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; EP, electrophysiological study.

9-year follow-up period than slower athletes.47 In the wider population, a U-shaped relationship is thought to exist between physical activity and AF incidence,46 48 where engagement in low-to-mod-erate physical activity reduces the risk of AF from a sedentary baseline but increasing doses, to the levels and intensity described above, may elevate risk. Presumably, modest physical activity is valu-able 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 remod-elling, 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 subse-quent establishment of AF.49 In reality, the patho-physiology of exercise-induced AF is likely to be multifactorial and may involve individual suscepti-bility factors that are yet to be discovered.50

Mature recreational athletes who develop AF without a substantial background of cumulative exercise should be evaluated for the conventional causes of AF, 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 review.10

IscHAemIc HeArt dIseAseAtherosclerotic CAD is a potentially fatal condi-tion facing athletes over 35 years of age.18 Seden-tary individuals, however, who have the most to gain from regular physical activity are paradoxi-cally at greater risk of exercise-associated cardiac arrest and myocardial infarction (MI) with vigorous exercise.7 8 51 A striking 9:1 male predominance is seen in SCD among competitive athletes52 and this increases to 20:1 among individuals engaged in recreational exercise,16 with large registries reporting proportions of 93%53–95%16 of SCDs occurring in men. Potential explanations for this sex discrepancy in SCDs include a relatively lower participation rate and engagement at lower inten-sity levels among women, although hormonal influ-ences cannot be disregarded.

The most common mode of SCD during sporting activity is an abrupt ventricular tachyarrhythmia.17 It is notable that many deaths in marathons occur in the final quartile of the event,52 54 suggesting that an elec-trolyte 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 stren-uous activity.55 It is possible that demand ischaemia,

5D'Silva A, Sharma S. Heart 2017;0:1–10. doi:10.1136/heartjnl-2016-310744

education in Heart

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 MI associated with vigorous physical exertion.56 For this reason, current recommendations from both the European Society of Cardiology (ESC)23 and the American Heart Association/American College of Cardiology (AHA/ACC)57 advocate risk stratification for recur-rent 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 ventricular ejection fraction <50%, haemo-dynamically significant coronary stenosis, exer-cise-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 stabilised and at least 3 months after an acute MI or coronary revascular-isation procedure.

Of paramount importance is compliance with opti-mised 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 signif-icant 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-MI,58–60 in asymptomatic, fully revascularised, low-risk patients, strong argu-ments can be made to individualise treatment on the basis of symptoms and tolerability.61–63

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 statins.64 65 The importance of lifelong compliance must be impressed on the athlete, as return to exercise is not an adequate substitute for evidence-based therapy.

Athletes may have concealed CAD, where they are asymptomatic though demonstrate unequivocal ischaemia during provocative testing coupled with angiographic evidence of haemodynamically signif-icant coronary artery stenosis. Such individuals should be risk stratified in same way as symptom-atic patients.

Finally, athletes with proven CAD who do not have haemodynamically significant coronary stenosis (<50% luminal narrowing), inducible ischaemia or complex ventricular arrhythmias on provoca-tive testing may undertake all competitive activities, provided resting left ventricular ejection fraction is >50% and there is adherence to medical therapy.57 These recommendations also apply to athletes with

coronary revascularisation and are summarised in figure 4. The most recent AHA/ACC recommenda-tions adopt a much more liberal position to compet-itive 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 compo-nents under previous Bethesda US guidelines.66 The new leniency is despite CAD being responsible for 80% of SCDs in mature athletes17 18 with no contem-porary evidence to support the safety of sports participation in this group. Communication with athletes with proven CAD should include explana-tion 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 scd In mAture AtHLetesGiven that the overwhelming majority of SCD affecting mature athletes are attributable to CAD, recommendations regarding preparticipation evaluation of mature athletes seem logical and prudent. Such recommendations have been devel-oped by the AHA67 and European Association of Cardiovascular Prevention and Rehabilitation (EACPR).68 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 physi-cian’s detailed cardiovascular evaluation is recom-mended 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 under-taking an increase in physical activity and the level of intensity of the intended activity. These addi-tions recognise that both factors contribute to SCD risk.7–9 16 Figure 5 summarises the EACPR recom-mendations in two management algorithms.69

Given the size of the population concerned and the lack of resources to support organised system-atic screening programmes 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 population.68 A physician-led cardiovas-cular evaluation includes history, physical examina-tion, estimation of 10 year cardiovascular risk using a validated scoring system70 71 and a resting ECG.

The value of maximal exercise testing for asymp-tomatic athletes at high cardiovascular risk in order to prevent SCD is more debatable. ECG exercise testing has established prognostic value,72–74 wide-spread availability and relatively low cost. Inducible

6 D'Silva A, Sharma S. Heart 2017;0:1–10. doi:10.1136/heartjnl-2016-310744

education in Heart

Figure 4 Diagnosis and management algorithm for athletes with cardiovascular conditions including which patients benefit from referral to tertiary level specialist centres. AV, atrioventricular; BP, blood pressure; CAD, coronary artery disease; EP, electrophysiological study; ICD, implantable cardioverter defibrillator; LBBB, left bundle branch block; LV EF, left ventricular ejection fraction; MI, myocardial infarction; 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 review.10

ischaemia and complex ventricular arrhythmias can be assessed simultaneously in a maximally toler-ated, 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 low,75

7D'Silva A, Sharma S. Heart 2017;0:1–10. doi:10.1136/heartjnl-2016-310744

education in Heart

Figure 5 European Association of Cardiovascular Prevention and Rehabilitation preparticipation cardiovascular evaluation protocol for asymptomatic sedentary adult/senior individuals (A) and active adult/senior individuals (B). Hx, history; Phys.exam., physical examination. Reproduced with permission from Corrado et al.69

with 18% sensitivity and 92% specificity,72 largely owing to low disease prevalence in a relatively healthy population. False-positive exercise tests are also a considerable problem, particularly for older athletes76 and women,77 78 and generate additional diagnostic testing with associated cost and anxiety. Diagnostic ischaemic ECG changes develop at an advanced stage of the ischaemia cascade and indi-cate the presence of haemodynamically signifi-cant coronary stenosis. Plaque rupture resulting in arrhythmic SCD, however, can occur in coronary lesions with only mild-to-moderate stenosis,79 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 have supranormal coronary perfusion reserve80; endurance training significantly improves endothe-lial function,81 and higher intensity exercise stim-ulates coronary artery collateral growth.82 These phenomena may account for atypical presentations of CAD in endurance athletes, who may experience only breathlessness or reduced exercise perfor-mance, 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 (CTCA), based on a wealth of anec-dotal experience of athletes with reduced perfor-mance and normal exercise tests but with severe CAD at coronary angiography.

Future dIrectIons In tHe mAnAgement oF mAture AtHLetesGiven 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 CTCA may be effective screening

tools in mature athletes. CACS and CTCA have proven predictive value for MI and SCD over clin-ical risk stratification.83 84 In a recent study of 318 asymptomatic male athletes aged over 45 years, CT identified occult CAD in 19%, where exer-cise ECG testing was negative during a high work load.85 Other studies suggest that CACS improves prediction of MI or death due to CAD only in intermediate-risk patients (Framingham Risk Score 10%–20%)86 but adds no predictive power for those with low risk (Framingham Risk Score <10%) as assessed by traditional cardiovascular disease risk factors.86–88 There are, in addition, implications of cost-effectiveness, radiation exposure, 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 calci-fication.85 89 Whether this translates to hard clin-ical 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 type.90 91 In contrast, relatively sedentary individuals with similarly low Framingham scores show a greater proportions of mixed morphology and soft plaques that are more vulnerable to rupture.91

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 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, midmyocardial, patchy distribu-tion, 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 caution.89

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

8 D'Silva A, Sharma S. Heart 2017;0:1–10. doi:10.1136/heartjnl-2016-310744

education in Heart

key messages

► Exercise is overwhelmingly beneficial for cardiovascular health, though vigorous intensity activity transiently elevates the risk of sudden cardiac death (SCD) for a small number of individuals with underlying cardiac conditions.

► Bradycardia and conduction blocks are common in athletes, but high degree atrioventricular 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.

cme credits for education in Heart

Education in Heart articles are accredited for CME by various providers. To answer the accompanying multiple choice questions (MCQs) and obtain your credits, click on the ‘Take the Test’ link on the online version of the article. The MCQs are hosted on BMJ Learning. All users must complete a one-time registration on BMJ Learning and subsequently log in on every visit using their username and password to access modules and their CME record. Accreditation is only valid for 2 years from the date of publication. Printable CME certificates are available to users that achieve the minimum pass mark.

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 expo-sure.92–94 Our own experience suggests that focal fibrosis in the region of the right ventricular inser-tion 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.

concLusIonMature 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 tran-siently elevate the acute risk of SCD in predisposed individuals. IHD is responsible for the majority of deaths among mature athletes, and men possess a ninefold 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, effec-tive preparticipation 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-as-sociated cardiac events in mature athletes and to establish whether high volume accumulated exer-cise exposure has clinically important sequelae. Athletes with hypertension and hypercholestero-laemia may experience troublesome adverse effects on treatment and therefore medications should be personalised depending on choices available and according to patient risk/benefit profile.

contributors AD wrote the article. SS edited the article and provided critical review, also contributed original material to the final manuscript.

competing interests AD was supported by a research grant from the charitable organization Cardiac Risk in the Young (CRY), which supports cardiovascular screening of young individuals. SS has been co-applicant on previous grants with CRY.

provenance and peer review Commissioned; externally peer reviewed.

Author note References marked with a * are key references for this paper.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

reFerences 1 Nocon M, Hiemann T, Müller-Riemenschneider F, et al. Association

of physical activity with all-cause and cardiovascular mortality: a systematic review and meta-analysis. Eur J Cardiovasc Prev Rehabil 2008;15:239–46.

2 Moore SC, Lee IM, Weiderpass E, et al. Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults. JAMA Intern Med 2016;176:816.

3 McTiernan A, Kooperberg C, White E, et al. Recreational physical activity and the risk of breast cancer in postmenopausal women: the women’s health initiative cohort study. JAMA 2003;290:1331–6.

4 Hamer M, Lavoie KL, Bacon SL. Taking up physical activity in later life and healthy ageing: the english longitudinal study of ageing. Br J Sports Med 2014;48:239–43.

5 Taylor RS, Brown A, Ebrahim S, et al. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials. Am J Med 2004;116:682–92.

6 Warburton DE, Charlesworth S, Ivey A, et al. A systematic review of the evidence for Canada’s physical activity guidelines for adults. Int J Behav Nutr Phys Act 2010;7:39.

7 Albert CM, Mittleman MA, Chae CU, et al. Triggering of sudden death from cardiac causes by vigorous exertion. N Engl J Med 2000;343:1355–61.

8 Siscovick DS, Weiss NS, Fletcher RH, et al. The incidence of primary cardiac arrest during vigorous exercise. N Engl J Med 1984;311:874–7.

9 Mittleman MA, Maclure M, Tofler GH, et al. Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of myocardial infarction onset study investigators. N Engl J Med 1993;329:1677–83.

10 D’Silva A, Sharma S. Management of young competitive athletes with cardiovascular conditions. Heart 2017;103:463–73.

11 Corrado D, Pelliccia A, Bjørnstad HH, et al. Cardiovascular pre-participation screening of young competitive athletes for prevention of sudden death: proposal for a common European protocol. Consensus statement of the study group of sport cardiology of the working group of cardiac rehabilitation and exercise physiology and the working Group of Myocardial and pericardial diseases of the European Society of Cardiology. Eur Heart J 2005;26:516–24.

12 Maron BJ, Thompson PD, Ackerman MJ, et al. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association

9D'Silva A, Sharma S. Heart 2017;0:1–10. doi:10.1136/heartjnl-2016-310744

education in Heart

Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 2007;115:1643–1455.

13 Van Brabandt H, Desomer A, Gerkens S, et al. Harms and benefits of screening young people to prevent sudden cardiac death. BMJ 2016;353:i1156.

14 Corrado D, Pelliccia A, Heidbuchel H, et al. Recommendations for interpretation of 12-lead electrocardiogram in the athlete. Eur Heart J 2010;31:243–59.

15 Harmon KG, Zigman M, Drezner JA. The effectiveness of screening history, physical exam, and ECG to detect potentially lethal cardiac disorders in athletes: a systematic review/meta-analysis. J Electrocardiol 2015;48:329–38. 2015.

*16 Marijon E, Tafflet M, Celermajer DS, et al. Sports-related sudden death in the general population. Circulation 2011;124:672–81.

17 Marijon E, Uy-Evanado A, Reinier K, et al. Sudden cardiac arrest during sports activity in middle age. Circulation 2015;131:1384–91.

18 Maron BJ, Epstein SE, Roberts WC. Causes of sudden death in competitive athletes. J Am Coll Cardiol 1986;7:204–14.

19 La Gerche A, Baggish AL, Knuuti J, et al. Cardiac imaging and stress testing asymptomatic athletes to identify those at risk of sudden cardiac death. JACC Cardiovasc Imaging 2013;6:993–1007.

20 Ljungqvist A, Jenoure P, Engebretsen L, et al. The International Olympic Committee (IOC) Consensus statement on periodic health evaluation of elite athletes March 2009. Br J Sports Med 2009;43:631–43.

21 Black HR, Sica D, Ferdinand K, et al. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 6: hypertension: A Scientific statement from the American Heart Association and the American College of Cardiology. J Am Coll Cardiol 2015;66:2393–7.

22 Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013;34:2159–219.

*23 Pelliccia A. Recommendations for competitive sports participation in athletes with cardiovascular disease: a consensus document from the study group of sports cardiology of the working group of cardiac rehabilitation and exercise physiology and the working group of myocardial and pericardial diseases of the european society of cardiology. Eur Heart J 2005;26:1422–45.

24 Brosnan M, La Gerche A, Kalman J, et al. Comparison of frequency of significant electrocardiographic abnormalities in endurance versus nonendurance athletes. Am J Cardiol 2014;113:1567–73.

25 Sharma S, Whyte G, Elliott P, et al. Electrocardiographic changes in 1000 highly trained junior elite athletes. Br J Sports Med 1999;33:319–24.

26 Boyett MR. ’And the beat goes on.’ The cardiac conduction system: the wiring system of the heart. Exp Physiol 2009;94:1035–49.

27 D’Souza A, Bucchi A, Johnsen AB, et al. Exercise training reduces resting heart rate via downregulation of the funny channel HCN4. Nat Commun 2014;5:3775.

28 Monfredi O, Dobrzynski H, Mondal T, et al. The anatomy and physiology of the sinoatrial node--a contemporary review. Pacing Clin Electrophysiol 2010;33:1392–406.

29 Boyett MR, D’Souza A, Zhang H, et al. Viewpoint: is the resting bradycardia in athletes the result of remodeling of the sinoatrial node rather than high vagal tone? J Appl Physiol 2013;114:1351–5.

30 Viitasalo MT, Kala R, Eisalo A. Ambulatory electrocardiographic recording in endurance athletes. Br Heart J 1982;47:213–20.

31 Bjørnstad H, Storstein L, Meen HD, et al. Ambulatory electrocardiographic findings in top athletes, athletic students and control subjects. Cardiology 1994;84:42–50.

32 Senturk T, Xu H, Puppala K, et al. Cardiac pauses in competitive athletes: a systematic review examining the basis of current practice recommendations. Europace 2016;18:euv373.

33 Barra SN, Providência R, Paiva L, et al. A review on advanced atrioventricular block in young or middle-aged adults. Pacing Clin Electrophysiol 2012;35:1395–405.

34 Kandolin R, Lehtonen J, Kupari M. Cardiac sarcoidosis and giant cell myocarditis as causes of atrioventricular block in young and middle-aged adults. Circ Arrhythm Electrophysiol 2011;4:303–9.

35 Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm

Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol 2008;51:e1–62.

36 Sheikh N, Sharma S. A young athlete with bradycardia. BMJ 2013;347:f4258.

37 Zipes DP, Link MS, Ackerman MJ, et al. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 9: arrhythmias and conduction defects: a scientific statement from the american heart association and american college of cardiology. J Am Coll Cardiol 2015;66:2412–23.

38 Kim JH, Noseworthy PA, McCarty D, et al. Significance of electrocardiographic right bundle branch block in trained athletes. Am J Cardiol 2011;107:1083–9.

*39 Sharma S, Drezner JA, Baggish A, et al. International recommendations for electrocardiographic interpretation in athletes. Eur Heart J 2017(Epub ahead of print 20 Feb 2017).

40 Lampert R, Olshansky B, Heidbuchel H, et al. Safety of sports for athletes with implantable cardioverter-defibrillators: results of a prospective, multinational registry. Circulation 2013;127:2021–30.

41 Abdulla J, Nielsen JR. Is the risk of atrial fibrillation higher in athletes than in the general population? A systematic review and meta-analysis. Europace 2009;11:1156–9.

42 Baldesberger S, Bauersfeld U, Candinas R, et al. Sinus node disease and arrhythmias in the long-term follow-up of former professional cyclists. Eur Heart J 2008;29:71–8.

43 Myrstad M, Nystad W, Graff-Iversen S, et al. Effect of years of endurance exercise on risk of atrial fibrillation and atrial flutter. Am J Cardiol 2014;114:1229–33.

44 Karjalainen J, Kujala UM, Kaprio J, et al. Lone atrial fibrillation in vigorously exercising middle aged men: case-control study. BMJ 1998;316:1784–5.

45 Mont L, Sambola A, Brugada J, et al. Long-lasting sport practice and lone atrial fibrillation. Eur Heart J 2002;23:477–82.

46 Calvo N, Ramos P, Montserrat S, et al. Emerging risk factors and the dose-response relationship between physical activity and lone atrial fibrillation: a prospective case-control study. Europace 2016;18:57–63.

47 Andersen K, Farahmand B, Ahlbom A, et al. Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study. Eur Heart J 2013;34:3624–31.

48 Morseth B, Graff-Iversen S, Jacobsen BK, et al. Physical activity, resting heart rate, and atrial fibrillation: the Tromsø Study. Eur Heart J 2016;37:2307–13.

49 Shen MJ, Choi EK, Tan AY, et al. Neural mechanisms of atrial arrhythmias. Nat Rev Cardiol 2011;9:30–9.

50 Guasch E, Mont L. Diagnosis, pathophysiology, and management of exercise-induced arrhythmias. Nat Rev Cardiol 2017;14:88–101.

51 Willich SN, Lewis M, Löwel H, et al. Physical exertion as a trigger of acute myocardial infarction. Triggers and Mechanisms of Myocardial Infarction Study Group. N Engl J Med 1993;329:1684-90.

*52 Kim JH, Malhotra R, Chiampas G, et al. Cardiac arrest during long-distance running races. N Engl J Med 2012;366:130–40.

53 Berdowski J, de Beus MF, Blom M, et al. Exercise-related out-of-hospital cardiac arrest in the general population: incidence and prognosis. Eur Heart J 2013;34:3616–23.

54 Redelmeier DA, Greenwald JA. Competing risks of mortality with marathons: retrospective analysis. BMJ 2007;335:1275–7.

55 Burke AP, Farb A, Malcom GT, et al. Plaque rupture and sudden death related to exertion in men with coronary artery disease. JAMA 1999;281:921–6.

56 Williams PT, Thompson PD. Increased cardiovascular disease mortality associated with excessive exercise in heart attack survivors. Mayo Clin Proc 2014;89:1187–94.

*57 Thompson PD, Myerburg RJ, Levine BD, et al. Eligibility and disqualification recommendations for competitive athletes with Cardiovascular Abnormalities: Task Force 8: Coronary Artery Disease: A Scientific Statement from the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015;66:2406–11.

58 Smith SC, Benjamin EJ, Bonow RO, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American

10 D'Silva A, Sharma S. Heart 2017;0:1–10. doi:10.1136/heartjnl-2016-310744

education in Heart

College of Cardiology Foundation endorsed by the World Heart Federation and the Preventive Cardiovascular Nurses Association. J Am Coll Cardiol 2011;58:2432–46.

59 Steg PG, James SK, Atar D, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;33:2569–619.

60 Chen ZM, Pan HC, Chen YP, et al. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005;366:1622–32.

61 Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2016;37:267–315.

62 Bangalore S, Steg G, Deedwania P, et al. β-Blocker use and clinical outcomes in stable outpatients with and without coronary artery disease. JAMA 2012;308:1340–9.

63 Puymirat E, Riant E, Aissoui N, et al. β blockers and mortality after myocardial infarction in patients without heart failure: multicentre prospective cohort study. BMJ 2016;354:i4801.

64 Sinzinger H, O’Grady J. Professional athletes suffering from familial hypercholesterolaemia rarely tolerate statin treatment because of muscular problems. Br J Clin Pharmacol 2004;57:525–8.

65 Meador BM, Huey KA. Statin-associated myopathy and its exacerbation with exercise. Muscle Nerve 2010;42:469–79.

66 Thompson PD, Balady GJ, Chaitman BR, et al. Task Force 6: coronary artery disease. J Am Coll Cardiol 2005;45:1348–53.

67 Maron BJ, Araújo CG, Thompson PD, et al. Recommendations for preparticipation screening and the assessment of cardiovascular disease in masters athletes: an advisory for healthcare professionals from the working groups of the World Heart Federation, the International Federation of Sports Medicine, and the American Heart Association Committee on Exercise, Cardiac Rehabilitation, and Prevention. Circulation 2001;103:327–34.

68 Borjesson M, Urhausen A, Kouidi E, et al. Cardiovascular evaluation of middle-aged/ senior individuals engaged in leisure-time sport activities: position stand from the sections of exercise physiology and sports cardiology of the European Association of Cardiovascular Prevention and Rehabilitation. Eur J Cardiovasc Prev Rehabil 2011;18:446–58.

69 Corrado D, Schmied C, Basso C, et al. Risk of sports: do we need a pre-participation screening for competitive and leisure athletes? Eur Heart J 2011;32:934–44.

70 Conroy RM, Pyörälä K, Fitzgerald AP, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J 2003;24:987–1003.

71 Balady GJ, Larson MG, Vasan RS, et al. Usefulness of exercise testing in the prediction of coronary disease risk among asymptomatic persons as a function of the Framingham risk score. Circulation 2004;110:1920–5.

72 Siscovick DS, Ekelund LG, Johnson JL, et al. Sensitivity of exercise electrocardiography for acute cardiac events during moderate and strenuous physical activity. The Lipid Research Clinics Coronary Primary Prevention Trial. Arch Intern Med 1991;151:325–30.

73 Gibbons LW, Mitchell TL, Wei M, et al. Maximal exercise test as a predictor of risk for mortality from coronary heart disease in asymptomatic men. Am J Cardiol 2000;86:53–8.

74 Laukkanen JA, Kurl S, Lakka TA, et al. Exercise-induced silent myocardial ischemia and coronary morbidity and mortality in middle-aged men. J Am Coll Cardiol 2001;38:72–9.

75 van de Sande DA, Breuer MA, Kemps HM. Utility of exercise electrocardiography in pre-participation screening in asymptomatic athletes: A Systematic Review. Sports Med 2016; 46:1155–64.

76 van de Sande DA, Hoogeveen A, Hoogsteen J, et al. The diagnostic accuracy of exercise electrocardiography in asymptomatic recreational and competitive athletes. Scand J Med Sci Sports 2016;26:214–20.

77 Kwok Y, Kim C, Grady D, et al. Meta-analysis of exercise testing to detect coronary artery disease in women. Am J Cardiol 1999;83:660–6.

78 Kohli P, Gulati M. Exercise stress testing in women: going back to the basics. Circulation 2010;122:2570–80.

79 Stone GW, Maehara A, Lansky AJ, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med 2011;364:226–35.

80 Hildick-Smith DJ, Johnson PJ, Wisbey CR, et al. Coronary flow reserve is supranormal in endurance athletes: an adenosine transthoracic echocardiographic study. Heart 2000;84:383–9.

81 Hambrecht R, Wolf A, Gielen S, et al. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N Engl J Med 2000;342:454–60.

82 Möbius-Winkler S, Uhlemann M, Adams V, et al. Coronary collateral growth induced by physical exercise: results of the impact of intensive exercise training on coronary collateral circulation in patients with stable coronary artery disease (EXCITE) trial. Circulation 2016;133:1438–48. discussion 48.

83 Arad Y, Goodman KJ, Roth M, et al. Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study. J Am Coll Cardiol 2005;46:158–65.

84 Detrano R, Guerci AD, Carr JJ, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med 2008;358:1336–45.

85 Braber TL, Mosterd A, Prakken NH, et al. Occult coronary artery disease in middle-aged sportsmen with a low cardiovascular risk score: the measuring athlete’s risk of cardiovascular events (MARC) study. Eur J Prev Cardiol 2016;23:1677–84.

86 Greenland P, LaBree L, Azen SP, et al. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. JAMA 2004;291:210–5.

87 Polonsky TS, McClelland RL, Jorgensen NW, et al. Coronary artery calcium score and risk classification for coronary heart disease prediction. JAMA 2010;303:1610–6.

88 Erbel R, Möhlenkamp S, Moebus S, et al. Coronary risk stratification, discrimination, and reclassification improvement based on quantification of subclinical coronary atherosclerosis: the Heinz Nixdorf Recall Study. J Am Coll Cardiol 2010; 56:1397–406.

89 Möhlenkamp S, Lehmann N, Breuckmann F, et al. Running: the risk of coronary events : prevalence and prognostic relevance of coronary atherosclerosis in marathon runners. Eur Heart J 2008;29:1903–10.

90 Aengevaeren VL, Mosterd A, Braber TL, et al. Relationship between lifelong exercise volume and coronary atherosclerosis in athletes. Circulation 2017;136:138–48.

*91 Merghani A, Maestrini V, Rosmini S, et al. Prevalence of subclinical coronary artery disease in masters endurance athletes with a low atherosclerotic risk profile. Circulation 2017;136:126–37.

92 Breuckmann F, Möhlenkamp S, Nassenstein K, et al. Myocardial late gadolinium enhancement: prevalence, pattern, and prognostic relevance in marathon runners. Radiology 2009;251:50–7.

93 La Gerche A, Burns AT, Mooney DJ, et al. Exercise-induced right ventricular dysfunction and structural remodelling in endurance athletes. Eur Heart J 2012;33:998–1006.

94 Wilson M, O’Hanlon R, Prasad S, et al. Diverse patterns of myocardial fibrosis in lifelong, veteran endurance athletes. J Appl Physiol 2011;110:1622–6.

PP-PFE-PAK

-006

9