Share this article on:

00005768-200808000-0001100005768_2008_40_1416_whyte_significance_8report< 120_0_12_3 >Medicine & Science in Sports & Exercise©2008The American College of Sports MedicineVolume 40(8)August 2008pp 1416-1423Clinical Significance of Cardiac Damage and Changes in Function after Exercise[CLINICAL SCIENCES: Symposium: Exercise and the Heart]WHYTE, GREGORY P.Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, UNITED KINGDOMAddress for correspondence: Gregory P. Whyte, Ph.D., FACSM, Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, L3 2ET, United Kingdom; E-mail: for publication December 2007.Accepted for publication March 2008.ABSTRACTAcute bouts of ultraendurance exercise may result in the appearance of biomarkers of cardiac cell damage and a transient reduction in left ventricular function. The clinical significance of these changes is not fully understood. There seems to be two competing issues to be resolved. First, could prolonged endurance exercise produce a degree of cardiac stress and/or damage that results, during the short or long term, in deleterious consequences for cardiac health. Second, there is a clear need to educate those responsible for the medical care of endurance athletes about the possibility of a transient reduction in cardiac function and the appearance of cTnT/cTnI after an exercise. Minor elevations in cardiac troponins are commonplace after an endurance exercise in elite and recreational athletes and may occur alongside exercise-associated collapse. Misdiagnosis of myocardial injury and subsequent mismanagement can be unnecessarily expensive and psychologically damaging to the athlete. Diagnosis of myocardial injury after prolonged exercise should be made on the basis of all available information and not blood tests alone. The clinical significance of chronic exposure to endurance exercise is unknown. The development of myocardial fibrosis has been suggested as a long-term outcome to chronic exposure to repetitive bouts of endurance exercise and has been linked to an exercise-induced inflammatory process observed in an animal model. This hypothesis is supported by a limited number of studies reporting postmortem studies in athletes and an increased prevalence of complex arrhythmia in veteran athletes. Care is warranted in promoting this hypothesis without further detailed work, given the unequivocal link between exercise and mortality and morbidity. It would seem erroneous, however, to assume that a linear relationship exists between exercise volume and cardiac health.Recent work from our laboratory, and others, has suggested that acute bouts of ultraendurance exercise may result in the appearance of biomarkers of cardiac cell damage in the systemic circulation and a transient reduction in the left ventricular (LV) function (9,23,27,36,49,50,56). Establishing the clinical significance of changes in cardiac biomarkers and function after acute and chronic endurance exercise is important in the management of the endurance athlete.There seems to be two competing but equally important issues that scientists and clinicians must resolve. First, could prolonged endurance exercise produce a degree of cardiac stress and/or damage that results, during the short or long term, in deleterious consequences for the health of the heart. This requires further analysis of the current cardiac biomarker literature, reflection on cohort, case study data related to topics such as sudden cardiac death, and ongoing empirical data collection. Furthermore, this necessitates an evaluation of broader aspects of cardiovascular health in the athlete with a lifetime history of endurance exercise exposure. Clearly, interpretation and speculation must adequately reflect a risk/benefit analysis that includes the beneficial effects of moderate physical activity in reducing cardiovascular mortality and morbidity (12). Baseless speculation and scaremongering could have a profoundly negative impact on the uptake of physical activity in the general population. Second, there is a clear need from a clinical perspective to educate those responsible for the medical care of endurance athletes about the possibility of a transient reduction in cardiac function and the appearance of cTnT/cTnI in the systemic circulation. Case study evidence suggests that cTnT/cTnI detected in blood samples after an event, associated with other signs and symptoms of the athletic heart (mimicking cardiac disease), may prompt significant medical intervention when, physiologically, these signs and symptoms may be entirely normal and indeed common. A vivid example of the necessity for raising awareness in this field is provided.Clinical Significance of Acute Elevations in Cardiac TroponinsMinor elevations in cardiac troponins are commonplace after endurance exercise in elite and recreational athletes and may occur alongside exercise-associated collapse after an endurance exercise. The collapse of an athlete concomitant to minor elevations in cardiac troponins and ECG anomalies commonly observed in athletes, particularly rapid uptake of the ST segment (ST elevation), may lead to the inappropriate provision of care. We recently described the inappropriate provision of care in a triathlete immediately after the successful completion of an Ironman triathlon (58). After a postrace massage and prolonged standing in the heat, the athlete reported presyncopal symptoms and collapsed without syncope. Blood pressure was measured at 75/40 mm Hg, and after fluid resuscitation, the athlete was referred to the cardiology department of the local hospital. The athlete was conscious and alert with normal core temperature, blood glucose, and plasma sodium and was otherwise asymptomatic. On admission, his ECG demonstrated minor ST segment elevation in the anterior lateral and inferior leads, and his cTnI was mildly elevated at 0.06 U·L−1. Echocardiography was normal with mild, concentric left ventricular hypertrophy (LVH). The athlete underwent diagnostic cardiac catheterization, which demonstrated normal coronary arteries. On the basis of the mildly elevated cTnI and minor ST segment elevation, the athlete was diagnosed with mild myopericarditis and advised to avoid exercise for 6 wk. On follow-up, 2 wk after being discharged from hospital, the resting 12-lead ECG demonstrated similar findings of marginal ST segment elevation in anterior lateral and inferior leads. Echocardiography demonstrated mild concentric left ventricular hypertrophy (12 mm) in the presence of normal diastolic and systolic function. There was no evidence of myocarditis or pericarditis, and the athlete was immediately cleared for training and competition.It is entirely possible that acute elevations of cardiac troponins are likely to be physiological in nature because of their rapid appearance and return to baseline (<24 h), the generally low values observed, and the lack of other signs and symptoms of cardiac disease. Therefore, they may, have little or no clinical significance. Indeed, some authors have suggested that their release may, in part, be related to the regulatory process of cardiac adaptation to exercise (48). The appearance and removal of cardiac troponins in athletes are normally in contrast to the kinetics of cardiac troponin release observed after myocardial infarction, where an initial release of unbound (cytosolic) troponin is followed by a continued release of the structurally bound troponin as it degrades, resulting in a sustained elevation in circulating troponin for many days after infarction (37). Accordingly, the use of one-off measures of cardiac troponins should be viewed with caution after prolonged exercise. Serial measures of cTnT/cTnI after exercise may assist in the differentiation of underling physiologic versus pathologic mechanisms, but this has rarely been reported. Misdiagnosis of myocardial injury after ultra-endurance exercise and subsequent mismanagement including hospitalization and invasive intervention can be unnecessarily expensive and psychologically damaging to the athlete. Diagnosis of myocardial injury after prolonged exercise should be made on the basis of all available information and not blood tests alone.The underlying mechanism(s) responsible for exercise-induced cTnT release is unknown. Furthermore, the long-term impact and clinical significance of chronic exposure to elevations in cTnT on the heart is unclear. On this basis, we cannot provide any strong conclusion as to the immediate or short-term clinical significance of elevated cardiac troponins associated with bouts of prolonged exercise.CLINICAL SIGNIFICANCE OF CHRONIC EXPOSURE TO ENDURANCE EXERCISEEndurance exercise and reactive scar tissue formation.The "leap" from cardiac responses to individual bouts of prolonged exercise to the consequences of chronic exposure to such training is not straightforward, and prospective data are limited. Despite this, the concept that individual bouts of exercise, producing cTnT/cTnI release, reflects minor but irreversible cardiomyocyte damage has been proposed by many studies that have suggested that endurance exercise may lead to scar tissue formation in the myocardium (23,24,26,42,52,54,59). The development of myocardial fibrosis has been linked to an exercise-induced inflammatory process observed in an animal model (6). It is pertinent to prompt some debate and further research to inform current understanding of the clinical significance of chronic exposure to endurance exercise.Two hypotheses for the significance of the minor myocardial injury, evidenced by elevated cardiac troponins, observed after prolonged endurance exercise have been proposed in the literature (24,44). Myocardial injury with exercise is reversible and followed by repair and results in myocyte hypertrophy. This process is analogous to the process involved in the response of skeletal muscle to training and is termed "supercompensation" (61). Thus, this hypothesis contends that myocardial injury is a physiological signal for adaptation leading to an enhanced structure and function. In contrast, a second hypothesis (44) suggests that myocardial injury is followed by scarring leading to fibrotic replacement of the myocardium that is associated with an increased potential for arrhythmia generation. This hypothesis contends that myocardial damage leads to a pathologic process of myocardial replacement that may be deleterious to the heart.To provide more detail, Rowe (43) suggested that permanent cardiac damage could develop in some endurance athletes despite the absence of coronary atherosclerosis and ventricular hypertrophy proposing two physiologic "vicious cycles" that could lead to fibrotic replacement of the myocardium: 1) severe ischemia and high catecholamines and 2)coronary vasospasm and endothelial injury. Other suggested mechanisms with exercise included Mg2+ deficiency, elevated free fatty acids, and elevated free radicals. Of note, the author postulated that injury becomes permanent if there is insufficient time between repeated bouts of exercise. Evidence to support the notion of a pathologic process of fibrotic infiltrate after exercise is limited. A small number of animal and human studies have reported findings from acute and chronic exercise exposure that support this hypothesis.Animal studies.Chen et al. (6) examined the heart of rats after a forced swim for 3.5 or 5 h with 8% of body mass attached to their tails. The rats were killed immediately after exercise and histologic examination demonstrated localized myocyte damage demonstrated by interstitial inflammatory infiltrates consisting of neutrophils, lymphocytes, and histiocytes (Fig. 1). Again, care is warranted in the interpretation of this finding given the highly stressful environment induced with survival in this model. It is evident, however, that exercise per se is able to induce inflammatory changes within the myocardium, which may act as a substrate for fibrotic replacement of the myocardium. Another study reported findings from the hearts of five horses that died suddenly (22). Autopsy findings revealed foci of myocardial fibrosis in the right atrium, interatrial septum, interventricular septum, and the conduction system. The authors postulated a relationship between sudden cardiac death and fibrotic and/or fibroplastic lesions in the area of the atrioventricular bundle and bundle branches associated with exercise, regardless of age.FIGURE 1-Representative hematoxylin-eosin-stained cross section of LV. Damaged myocardial fibers and damaged intracellular areas are shown by foci of inflammatory infiltrates consisting of neutrophils, lymphocytes, and histiocytes (a) and vesicular nuclei-enlarged chromatin patterns (b) (6).Human studies.Limited premortem evidence exists to support the presence of cardiac fibrosis in athletes. A recent study reported a biochemical evidence for cardiac fibrosis in veteran endurance athletes (25). The authors suggested that the incomplete reversal of cardiac hypertrophy after cessation of exercise training observed in veteran athletes (34) is because of the presence of cardiac fibrosis. Using humeral collagen markers (TIMP-1, CITP, and PICP), the authors demonstrated an association between LVH and a disruption of the collagen equilibrium and suggested that this would favor the development of cardiac fibrosis in veteran athletes. Although interesting, care is warranted in the interpretation of the cause and effect from such relationships, and further studies are required to corroborate the findings.A small number of studies have reported fibrotic infiltrate in the hearts of trained endurance athletes at autopsy. Virmani et al. (52) reported autopsy findings in 30 joggers who suffered sudden cardiac death. Of 30 athletes, 7 (25%) had no identifiable cause of death at autopsy. Of these, three of the hearts were hypertrophied and six had evidence of myocytolysis and contraction band necrosis. The authors hypothesized that coronary vasospasm, possibly induced during the stress of exercise, leading to a cascade of ischemia, necrosis, and fibrosis, was a possible mechanism responsible for these findings.In one of the most prolifically cited papers on the subject, Rowe (42) reported on the death of a world-record marathon runner (cause of death: lymphoma). Premortem, the athlete had experienced episodes of angina, and in the presence of normal coronaries, had been diagnosed with circadian variation in the coronary vasospasm (Prinzmetal angina). At autopsy, small, patchy nontransmural scar in the LV posterior wall and focal fibrosis of the left papillary muscles consistent with remote ischemic insult were observed in the presence of normal coronaries and microvasculature. The author suggested that ischemia associated with coronary vasospasm was responsible for the observed scarring. The mechanism underlying the proposed coronary vasospasm remains unclear, although, exercise may play a critical role.A recent highly publicized study reported on the sudden cardiac death of 16 Swedish orienteers between the years 1979 and 1992 (7 occurring between 1989 and 1992) (54). Of 16 athletes, 5 presented with active myocarditis and 4 with arrhythmogenic right ventricular cardiomyopathy (ARVC)-like alterations in the right ventricle (RV). All athletes had undergone medical examination including ECG on entry to the Swedish military. Of the four athletes presenting with ARVC-like changes, only one athlete had received a follow-up evaluation after an episode of tachycardia. In the other three athletes, no cardiac signs or symptoms had been reported premortem. There was no family history of sudden unexplained death in any of the athletes. The etiology of the ARVC-like changes observed in these athletes is unclear; however, the absence of overt ARVC may suggest an exercise-mediated mechanism. Care is warranted, however, because first-degree relatives were not screened after the death of the athletes. Furthermore, the disease may have been in the early concealed phase of ARVC where identification is difficult (51).In a recent case study from our group, we reported on the presence of idiopathic interstitial myocardial fibrosis and idiopathic LVH (ILVH) at postmortem in the heart of an athlete that died suddenly during a marathon race (59). The deceased had been running for 20 yr, having completed multiple marathons, with a personal best time of 2 h 30 min. At autopsy, the weight of the heart was 480 g, which is above that expected for a 75-kg male (upper limit of 431 g), and there was widespread replacement fibrosis particularly in the lateral and posterior ventricular walls as well as interstitial fibrosis in the inner layer of the myocardium (Fig. 2). Premortem, the athlete was healthy and free from cardiovascular disease, and there was no documented evidence of diseases associated with widespread myocardial fibrosis. The cardiac pathologic findings were consistent with a left ventricular hypertrophy of indeterminate causation (also known as "idiopathic left ventricular hypertrophy," ILVH) in the presence of idiopathic interstitial fibrosis. ILVH has been previously documented in athletes at postmortem associated with sudden cardiac death (45,47). In an early study of 30 nontraumatic deaths, Virmani et al. (52) observed ILVH with coexiting myocytolysis and contraction band necrosis in three joggers. In addition, Maron and Roberts (29) reported a 7.5% incidence of ILVH at autopsy in athletes after sudden cardiac death.FIGURE 2-Widespread replacement fibrosis particularly in the lateral and posterior ventricular walls as well as interstitial fibrosis in the inner layer of the myocardium. Myocyte hypertrophy was observed around the areas of scarring but no myocyte disarray indicative of hypertrophic cardiomyopathy.In postulating a mechanism for the development of myocardial fibrosis, it is important to exclude known pathological substrates for its development. Widespread myocardial fibrosis is observed in healed myocarditis, dilated cardiomyopathy (28), hypertrophic cardiomyopathy, noninfarcted myocardium from hearts with ischemic scars (53), and systemic hypertension (40) and is rarely linked to small intramural coronary artery disease. An increased collagen content after Sirius red FB3 staining of the myocardium is also observed in the presence of inflammatory and amyloid cells and as a result of myocarditis at autopsy. Fibrosis creates a potential substrate for reentry, arrhythmia, and sudden cardiac death. Importantly, it is not the density of fibrosis that dictates the arrhythmia potential rather the position of fibrosis, i.e., near the conduction system and the architecture of fibrosis (19). Thus, a low density of patchy fibrosis may be sufficient to propagate fatal arrhythmias.The etiology of the fibrosis observed in the studies presented is unclear. The potential relationship between the elevated levels of the humeral markers of cardiac myocyte damage observed after acute bouts of prolonged exercise might suggest that chronic exposure to repeated bouts of minimal cardiac damage may result in the development of interstitial myocardial fibrosis in some individuals. Limited evidence to support this hypothesis exists in the literature, likely because of the absent histological examination of the hearts of athletes postmortem. Long-term follow-up of athletes and closer interrogation of veteran athletes may shed light of the impact of prolonged repetitive bouts of endurance exercise.Arrhythmia and the athlete.Previous studies have reported an increased incidence of supraventricular, complex ventricular, and profound bradyarrhythmias in veteran athletes (5,11,14-16,18,38). Although the underlying mechanism for this increased arrhythmia prevalence is not fully understood, it has been suggested that structural changes of the electrical conduction system and the myocardium including interstitial fibrosis may be responsible.Heidbuchel et al. (13) reported findings from 46 well-trained endurance athletes presenting with ventricular arrhythmia (VA). Eighty percent of the arrhythmias had a left bundle branch morphology and a RV arrhythmogenic involvement was manifest in 59% of athletes and suggestive in 30%. The prognosis for these athletes was poor with a sudden death incidence of 25% (all cyclists) in a 4.7-yr follow-up. The authors postulated that repeated RV insults may lead to chronic RV dysfunction providing a substrate for arrhythmia. Although the authors recognized that the pathophysiology of arrhythmias in endurance athletes is poorly understood, they hypothesized that long-lasting volume overload and a higher tendency to resort to performance enhancing drugs may play a role in revealing an underlying (genetic) substrate and/or in promoting the development of VA. This concept is supported by recent findings in a mouse model of ARVC. Kirchof et al. (21) demonstrated that heterozygous plakoglobin-deficient mice presented an accelerated development of RV dysfunction and arrhythmia in response to endurance training. Based on these findings, the term "exercise-induced ventricular dysplasia" was coined.Ector et al. (10) examined 22 endurance athletes presenting with VA. Findings suggested an RV arrhythmogenic origin in 82% of athletes with RV dysfunction as the predisposing substrate. The authors concluded that endurance exercise may act as a promoter for RV structural remodeling and a resultant trigger for VA. Some care is warranted in the interpretation of this finding. Several forms of idiopathic VA have been identified in athletes that, by definition, originate in hearts without structural abnormalities (2). The differentiation of pathological VA and benign VA originating in the RV is clinically important when discussing prognosis and management options (39). This is of particular importance in the differentiation of right ventricular outflow tract-ventricular tachycardia and arrythmogenic right ventricular cardiomyopathy (ARVC) given the association of the latter with sudden death in athletes (51). Long-standing VA can result in ventricular hypokinesis leading to dysfunction. It is important to note, however, that after cardioversion through pharmacologic or nonpharmacologic means, a normal function is often restored suggesting a nonpermanent cause of VA (57).The clinical significance of supraventricular, complex ventricular, and profound bradyarrhythmias remains to be fully elucidated. Evidence from Heidbuchel et al. (13) would support a potentially fatal outcome of complex VA in endurance athletes. Postmortem evidence of arrhythmic death in the absence of any other cause is difficult to collect, and very few studies have proposed an arrhythmic substrate as the cause of death. One study reporting the deaths of 60 squash players suggested an arrhythmic cause in 2 players (38). Unfortunately, the authors failed to describe how this conclusion was reached. Further studies are required to identify the underlying mechanisms of arrhythmia and their clinical significance in athletic populations.CLINICAL SIGNIFICANCE OF ACUTE CHANGES IN CARDIAC FUNCTION AFTER PROLONGED EXERCISEA small and transient depression in cardiac function is commonly observed after acute bouts of endurance exercise (33). The nature of these changes seems dependent on a number factors such as exercise duration (7,31,33,55). Whether the changes represent global or regional responses to the prolonged exercise is open to some debate (33), but evidence of regional dyskinesis has been reported (9,24,36,41). These findings offer some support for a "true," load-independent depression in LV function, which requires further investigation. The mechanisms underlying the observed dysfunction remain elusive (56), and the clinical consequences have yet to be fully evaluated. The time course of change in cardiac function after prolonged exercise is such that rapid recovery occurs normally within 24-48 h (7,31,33) and again supports the suggestion that the changes observed are physiological in nature. In this case, there may be limited clinical significance of such changes.A small number of studies have reported more prolonged changes in function. Neilan et al. (36) reported the persistence of diastolic changes 4 wk after a marathon in recreational runners. La Gerche and Prior (24) noted sustained RV dysfunction in one athlete at 7 d and 12 months after an Ironman triathlon. Occasionally, there have been case reports of a more profound acute impact of cardiac function. An early study reported pulmonary edema in two highly trained runners after an ultraendurance race. The authors suggested that RV dysfunction may have resulted in pulmonary congestion leading to pulmonary edema (32). This has prompted some specific interest in the response of the RV to bouts of prolonged exercise. The difficulty associated with imaging the RV has led to a preponderance of studies examining the left ventricle; however, the RV may be less able to compensate for the sustained elevation in cardiac output and/or pulmonary hypertension during prolonged exercise. In an early study, Douglas et al. (9) observed RV dilatation and segmental wall motion abnormalities in triathletes immediately after an Ironman triathlon. Davila-Roman et al. (8) examined cardiac function in 14 well-trained runners after a high- altitude ultraendurance run (163 km). Immediately after exercise, 35% (5/14) of runners presented with RV dilatation and dyskinesis. The authors concluded that an increased pulmonary artery systolic pressure (PASP) i.e., pulmonary hypertension was responsible for the observed changes. In a recent study, La Gerche et al. (23) examined cardiac function in 26 triathletes after an Ironman triathlon. The authors reported RV dysfunction in all subjects in the absence of change in PASP.These data prompted further study; however, there is some suggestion that some individuals have more marked or more clinically relevant changes in cardiac function after prolonged exercise. There may also be a genetic component in the presence of cardiac troponins and the level of cardiac dysfunction after an acute bout of endurance exercise (3). At this stage, again, we do not know what the long-term relevance of such changes are nor can we identify those individuals at greater risk. The development of our understanding of the mechanism(s) underlying the changes in LV and RV function after a single bout of endurance exercise will likely aid the development of understanding related to the notion that an acute bout of prolonged endurance exercise could have a prolonged deleterious effect on cardiac function.FUTURE DIRECTIONSFuture studies should examine the cardiac response to, and clinical significance of, repetitive bouts and lifelong participation in endurance exercise. Cross-sectional and prospective studies of veteran athletes engaged in lifelong endurance exercise may be valuable in elucidating the impact of repetitive cardiac insults imposed by endurance exercise.Further studies are required to examine the potential relationship between minimal cardiac damage, inflammation, and interstitial myocardial fibrosis. Within this quasiphysiologic milieu, inflammation may be the precursor of the observed fibrosis. Recently, cardiovascular magnetic resonance (CMR), by the technique of delayed myocardial contrast hyperenhancement, has been successfully used to visualize acute and chronic myocardial infarction (4,20,60). This technique relies on the difference between wash-in and wash-out kinetics and the volume of distribution of gadolinium in edematous/fibrotic myocardium. This technique shows promise in detecting causes of myocardial fibrosis including sarcoid, systemic sclerosis, hypertrophic cardiomyopathy, and dilated cardiomyopathy (30,35). In addition to the identification of interstitial fibrosis, work from our group has demonstrated a role for late gadolinium-enhanced CMR and STIR scans in the identification of myocardial inflammation (4). Future studies should aim to investigate the potential inflammatory effects of endurance exercise on the heart of humans.CONCLUSIONSA burgeoning body of literature supports a positive impact of moderate-intensity, moderate-duration exercise on mortality and morbidity. In contrast, little is known regarding the upper limit of exercise volume (intensity, frequency, and duration) for cardiac health. It would seem erroneous to assume that a linear relationship exists between exercise volume and cardiac health. A plateau or possible increased risk may be present with very high exercise volumes (Fig. 3).FIGURE 3-Hypothetical relationship between exercise volume and incidence of cardiac events.It is apparent from the literature that there exists the potential for a clinically relevant or pathological response to prolonged arduous exercise in a small number of individuals. This may qualitatively mirror other pathologies such as hyponatremia and malignant hypothermia where only a minority of exercisers are susceptible when the majority are unaffected. The heterogenous response to a combined exercise and environment stimulus may be underpinned by genetics (1,17). In light of the potential for a deleterious effect of endurance exercise on other systems, it would be naive to assume that the cardiovascular system in some individuals may not be susceptible to the rigors of prolonged arduous exercise.The author thanks Cardiac Risk in the Young for their support in the production of this article.The results and conclusions of the present study do not constitute endorsement by the ACSM.REFERENCES1. Ali S, Taguchi A, Rosenburg H. Malignant hyperthermia. Best Pract Res Clin Anaesthesiol. 2003;17:519-33. [CrossRef] [Medline Link] [Context Link]2. Anselme F. Association of idiopathic RVOT VT and AVNRT: anything else than chance. Europace. 2003;5:221-3. [CrossRef] [Medline Link] [Context Link]3. Ashley E, Kardos A, Fronning K, et al. ACE genotype predicts cardiac and autonomic responses to prolonged exercise. J Am Coll Cardiol. 2006;48:523-31. [Context Link]4. Babu-Narayan S, McCarthy K, Ho S, Magee A, Kilner P, Sheppard M. Myocarditis and sudden cardiac death in the young. Extensive fibrosis suggested by cardiovascular magnetic resonance in vivo and confirmed post mortem. Circulation. 2007;116:e122-5. [CrossRef] [Full Text] [Medline Link] [Context Link]5. Bjornstad H, Storstein L, Dyre H, Hals O. Electrocardiographic findings in left, right and septal hypertrophy in athletic students and sedentary controls. Cardiology. 1993;82:56-65. [CrossRef] [Medline Link] [Context Link]6. Chen Y, Serfass R, Mackey-Bojack S, Kelly K, Titus J, Apple F. Cardiac troponins T alterations in myocardium of serum of rats after stressful, prolonged intense exercise. J Appl Physiol. 2000;88:1749-55. [Medline Link] [Context Link]7. Dawson E, George KP, Shave R, Whyte G, Ball D. Does the heart fatigue subsequent to prolonged exercise in humans? Sports Med. 2003;33:365-80. [CrossRef] [Full Text] [Medline Link] [Context Link]8. Davila-Roman V, Guest T, Tuteur P, Rowe WJ, Ladenson J, Jaffe A. Transient right but not left ventricular function after strenuous exercise at high altitude. J Am Coll Cardiol. 1997;30:468-73. [CrossRef] [Medline Link] [Context Link]9. Douglas P, O'Toole ML, Hiller WD, Reichek N. Different effects of prolonged exercise on the right and left ventricles. J Am Coll Cardiol. 1990;15:64-9. [CrossRef] [Medline Link] [Context Link]10. Ector J, Ganame J, van der Merwe N, et al. Reduced right ventricular ejection fraction in endurance athletes presenting with ventricular arrhythmias: a quantitative angiographic assessment. Eur Heart J. 2007;28:345-53. [CrossRef] [Full Text] [Medline Link] [Context Link]11. Elosua R, Arquer A, Mont L, et al. Sports practice and the risk of lone atrial fibrillation: a case-control study. Int J Cardiol. 2006;108:332-7. [CrossRef] [Medline Link] [Context Link]12. Hahn R, Teutsch S, Paffenbarger R, Marks J. Excess deaths from nine chronic diseases in the United States. J Am Med Assoc. 1990;264:2654-9. [CrossRef] [Medline Link] [Context Link]13. Heidbuchel H, Hoogsteen J, Fagard R, Vanhees L, Ector H, Willems R. High prevalence of right ventricular involvement in endurance athletes with ventricular arrhythmias. Role of an electrophysiologic study in risk stratification. Eur Heart J. 2003;24:1473-80. [CrossRef] [Medline Link] [Context Link]14. Hood S, Northcote R. Cardiac assessment of veteran endurance athletes: a 12 year follow-up study. Br J Sports Med. 1999;33:239-43. [CrossRef] [Medline Link] [Context Link]15. Jensen-Ursted K, Errikson M, Saltin B. Pronounced resting bradycardia in male elite runners is associated with increased heart rate variability. Scand J Med Sci Sports. 1997;5:274-8. [Context Link]16. Jensen-Urstad K, Bouvier F, Saltin B, Jensen-Urstad M. High prevalence of arrhythmia in elderly male athletes with a lifelong history of regular strenuous exercise. Heart. 1998;79:161-4. [Context Link]17. Jones A, Montgomery H, Woods D. Human performance: a role for the ACE genotype? Exerc Sport Sci Rev. 2002;30(4):184-90. [CrossRef] [Full Text] [Medline Link] [Context Link]18. Karajalainen J, Kujala U, Kaprio J, Sarna S, Viitasalo M. Lone atrial fibrillation in vigorously exercising middle aged men: case-control study. BMJ. 1998;316:1784-5. [Context Link]19. Kawara T, Derksen R, de Groot J, et al. Activation delay after premature stimulation in chronically diseased human myocardium relates to the architecture of interstitial fibrosis. Circulation. 2001;104:3069-75. [CrossRef] [Full Text] [Medline Link] [Context Link]20. Kim RJ, Wu E, Rafael A. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med. 2000;343:1445-53. [CrossRef] [Full Text] [Medline Link] [Context Link]21. Kirchof P, Fabritz L, Zwiener M, et al. Age- and training-dependent development of arrhythmogenic right ventricular cardiomyopathy in heterozygous plakoglobin-deficient mice. Circulation. 2006;114:1799-806. [Context Link]22. Kiryu K, Machida N, Kashida Y, Yoshihara T, Amada A, Yamamoto T. Pathologic and electrocardiographic findings in sudden cardiac death in racehorses. J Vet Med Sci. 1999;61:921-8. [CrossRef] [Medline Link] [Context Link]23. La Gerche A, Connelly K, MacIsaac A, Mooney D, Prior D. Biochemical and functional abnormalities of left and right ventricular function following ultra-endurance exercise. Eur Heart J. 2007;[Epub ahead of print]. [Context Link]24. La Gerche A, Prior D. Exercise - is it possible to have too much of a good thing? Heart, Lung and Circulation. 2007;16(Suppl 3):S102-4. [Context Link]25. Lindsay M, Dunn G. Biochemical evidence of fibrosis in veteran endurance athletes. Br J Sports Med. 2007;41:447-52. [CrossRef] [Full Text] [Medline Link] [Context Link]26. Ludmerer K, Kissane G. Clinico-pathologic conference: sudden death in a 47 year old marathon runner. Am J Med. 1984;76:517-26. [Context Link]27. Mair J, Wohlfarter T, Koller A. Serum cardiac troponin T after extraordinary endurance exercise. Lancet. 1992;340:1048. [CrossRef] [Medline Link] [Context Link]28. Marijianowski M, Teeling P, Mann J. Dilated cardiomyopathy is associated with an increase in type I: type III collagen ratio. A quantitative assessment. J Am Coll Cardiol. 1995;25:1263-72. [CrossRef] [Medline Link] [Context Link]29. Maron BJ, Roberts WO. Risk of cardiac death associated with marathon running. J Am Coll Cardiol. 1996;28:428-31. [CrossRef] [Medline Link] [Context Link]30. McCrohon JA, Moon JC, Prasad SK. Differentiation of heart failure related to dilated cardiomyopathy and coronary artery disease using gadolinium-enhanced cardiovascular magnetic resonance. Circulation. 2003;108:54-9. [CrossRef] [Full Text] [Medline Link] [Context Link]31. McGavock JM, Warburton DE, Taylor D, Welsh RC, Quinney HA, Haykowsky MJ. The effects of prolonged strenuous exercise on left ventricular function: a brief review. Heart Lung. 2002;31:279-92. [CrossRef] [Full Text] [Medline Link] [Context Link]32. McKechnie JK, Lear WP, Noakes TD, Kallmeyer JC, MacSearraigh ET, Olivier LR. Acute pulmonary oedema in two athletes during a 90-km running race. S Afr Med J. 1979;56:261-5. [Medline Link] [Context Link]33. Middleton N, Shave R, George K, Whyte G, Hart E, Atkinson G. Echocardiographic examination of left ventricular function immediately following prolonged endurance exercise: a meta-analysis. Med Sci Sports Exerc. 2006;38(4):681-7. [Context Link]34. Miki T, Yokoto Y, Seo T. Echocardiographic findings in 104 professional cyclists with follow-up study. Am Heart J. 1994;127:898-905. [CrossRef] [Medline Link] [Context Link]35. Moon JC, Reed E, Sheppard M. The histologic basis of late gadolinium enhancement cardiovascular magnetic resonance inhypertrophic cardiomyopathy. J Am Coll Cardiol. 2004;43:2260-4. [CrossRef] [Medline Link] [Context Link]36. Neilan T, Yoerger D, Douglas P, et al. Persistent and reversible cardiac dysfunction among amateur marathon runners. Eur Heart J. 2006;27:1079-84. [CrossRef] [Full Text] [Medline Link] [Context Link]37. Newby NL. Markers of cardiac ischemia, injury, and inflammation. Prog Cardiovasc Dis. 2004;46:404-16. [CrossRef] [Medline Link] [Context Link]38. Northcote R, Canning G, Ballantyne D. Electrocardiographic findings in male veteran endurance athletes. Br Heart J. 1988;61:155-60. [Context Link]39. O'Donnell D, Cox D, Bourke L, Mitchell L, Furniss S. Clinical and electrophysiological differences between patients with arrhythmogenic right ventricular outflow tract tachycardia. Eur Heart J. 2003;24:801-10. [Context Link]40. Pardo-Mendaise F, Panizo A. Alterations in the extracellular matrix myocardium in essential hypertension. Eur Heart J. 1993;14:12-4. [Context Link]41. Rifai N, Douglas P, O'Toole M, Rimm E, Ginsburg G. Cardiac troponin T and I, echocardiographic wall motion analyses, and ejection fractions in athletes participating in the Hawaii Ironman Triathlon. Am J Cardiol. 1999;83:1085-89. [Context Link]42. Rowe WJ. A world record marathon runner with silent ischemia without coronary atherosclerosis. Chest. 1991;99:1306-8. [CrossRef] [Medline Link] [Context Link]43. Rowe WJ. Extraordinary unremitting endurance exercise and permanent injury to normal heart. Lancet. 1992;340:712-4. [CrossRef] [Medline Link] [Context Link]44. Rowe WJ. Endurance exercise and injury to the heart. Sports Med. 1993;16:73-9. [CrossRef] [Full Text] [Medline Link] [Context Link]45. Seto CK. Preparticipation cardiovascular screening. Clin Sports Med. 2003;22:23-35. [Context Link]46. Sharma S, Whyte G, Elliott P, et al. Electrocardiographic changes in 1000 highly trained elite athletes. Br J Sports Med. 1990;30:319-24.47. Sharma S, Whyte G, McKenna WJ. Sudden cardiac death in young athletes-fact or fiction? Br J Sports Med. 1997;31:269-76. [CrossRef] [Medline Link] [Context Link]48. Shave R, George K, Atkinson G, et al. Exercise induced cardiac troponin T release: a meta-analysis. Med Sci Sports Exerc. 2007;39(12):2099-106. [Context Link]49. Shave R, Dawson E, Whyte G, et al. Evidence of exercise-induced cardiac dysfunction and elevated cTnT in separate cohorts competing in an ultra-endurance mountain marathon race. Int J Sports Med. 2002;23:489-94. [CrossRef] [Medline Link] [Context Link]50. Shave RE, Whyte GP, George K, Gaze DC, Collinson PO. Prolonged exercise should be considered alongside typical symptoms of AMI when evaluating elevations in cardiac troponin T. Heart. 2005;I91:1219-20. [Context Link]51. Thiene G, Nava A, Corrado D, Rossi L, Pennelli N. Right ventricular cardiomyopathy and sudden death in young people. N Engl J Med. 1988;318:129. [CrossRef] [Medline Link] [Context Link]52. Virmani R, Robinowitz M, McAllister H. Nontraumatic death in joggers. A series of 30 patients at autopsy. Am J Med. 1982;72:874-82. [CrossRef] [Medline Link] [Context Link]53. Volders P, Willems I, Cleutjens J. Interstitial collagen is increased in the non infracted myocardium after myocardial infarction. J Mol Cell Cardiol. 1993;25:1317-23. [CrossRef] [Medline Link] [Context Link]54. Wesslen L, Pahlson C, Lindquist O, Hjelm E, Gnarpe J, Larsson E. An increase in sudden unexpected cardiac deaths among Swedish orienteers during 1979-1992. Eur Heart J. 1996;17:902-10. [CrossRef] [Medline Link] [Context Link]55. Whyte G, George K, Sharma S, et al. Cardiac fatigue following prolonged endurance exercise of differing distances. Med Sci Sports Exerc. 2000;32(6):1067-72. [CrossRef] [Full Text] [Medline Link] [Context Link]56. Whyte G, George K, Shave R, et al. The impact of marathon running on cardiac structure and function in recreational runners. Clin Sci. 2005;108:73-80. [CrossRef] [Medline Link] [Context Link]57. Whyte G, Sheppard M, George K, et al. Arrhythmias and the athlete: mechanisms and clinical significance. Eur Heart J. 2007;28:1399-401. [CrossRef] [Full Text] [Medline Link] [Context Link]58. Whyte G, Stephens N, Senior N, et al. Treat the patient not the blood test: the implications of an elevation in cardiac troponin following prolonged exercise. Br J Sports Med. 2007;[Epub ahead of print]. [Context Link]59. Whyte G, Sheppard M, George K, et al. Post-mortem evidence of idiopathic left ventricular hypertrophy and idiopathic interstitial myocardial fibrosis: is exercise the cause? Br J Sports Med. 2007;[Epub ahead of print] [Context Link]60. Wu E, Judd RM, Vargas JD. Visualisation of presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction. Lancet. 2001;357:21-8. [CrossRef] [Medline Link] [Context Link]61. Yakolev N, Kaledin S, Krasnova A, et al. Physiological and chemical adaptation to muscular activity in relation to the length of rest periods between exertions during training. Fiziol Zh SSSR Im I M Sechenova. 1961;47:56-9. [Medline Link] [Context Link] MYOCARDIAL FIBROSIS; ARRHYTHMIA; TROPONINS;|00005768-200808000-00011#xpointer(id(R1-11))|11065213||ovftdb|SL0013985320031751911065213P54[CrossRef]|00005768-200808000-00011#xpointer(id(R1-11))|11065405||ovftdb|SL0013985320031751911065405P54[Medline Link]|00005768-200808000-00011#xpointer(id(R2-11))|11065213||ovftdb|SL001270692003522111065213P55[CrossRef]|00005768-200808000-00011#xpointer(id(R2-11))|11065405||ovftdb|SL001270692003522111065405P55[Medline Link]|00005768-200808000-00011#xpointer(id(R4-11))|11065213||ovftdb|00003017-200708070-00019SL000030172007116e12211065213P57[CrossRef]|00005768-200808000-00011#xpointer(id(R4-11))|11065404||ovftdb|00003017-200708070-00019SL000030172007116e12211065404P57[Full Text]|00005768-200808000-00011#xpointer(id(R4-11))|11065405||ovftdb|00003017-200708070-00019SL000030172007116e12211065405P57[Medline Link]|00005768-200808000-00011#xpointer(id(R5-11))|11065213||ovftdb|SL000028421993825611065213P58[CrossRef]|00005768-200808000-00011#xpointer(id(R5-11))|11065405||ovftdb|SL000028421993825611065405P58[Medline Link]|00005768-200808000-00011#xpointer(id(R6-11))|11065405||ovftdb|SL00004560200088174911065405P59[Medline Link]|00005768-200808000-00011#xpointer(id(R7-11))|11065213||ovftdb|00007256-200333050-00003SL0000725620033336511065213P60[CrossRef]|00005768-200808000-00011#xpointer(id(R7-11))|11065404||ovftdb|00007256-200333050-00003SL0000725620033336511065404P60[Full Text]|00005768-200808000-00011#xpointer(id(R7-11))|11065405||ovftdb|00007256-200333050-00003SL0000725620033336511065405P60[Medline Link]|00005768-200808000-00011#xpointer(id(R8-11))|11065213||ovftdb|SL0000448119973046811065213P61[CrossRef]|00005768-200808000-00011#xpointer(id(R8-11))|11065405||ovftdb|SL0000448119973046811065405P61[Medline Link]|00005768-200808000-00011#xpointer(id(R9-11))|11065213||ovftdb|SL000044811990156411065213P62[CrossRef]|00005768-200808000-00011#xpointer(id(R9-11))|11065405||ovftdb|SL000044811990156411065405P62[Medline Link]|00005768-200808000-00011#xpointer(id(R10-11))|11065213||ovftdb|00003628-200728030-00015SL0000362820072834511065213P63[CrossRef]|00005768-200808000-00011#xpointer(id(R10-11))|11065404||ovftdb|00003628-200728030-00015SL0000362820072834511065404P63[Full Text]|00005768-200808000-00011#xpointer(id(R10-11))|11065405||ovftdb|00003628-200728030-00015SL0000362820072834511065405P63[Medline Link]|00005768-200808000-00011#xpointer(id(R11-11))|11065213||ovftdb|SL00004337200610833211065213P64[CrossRef]|00005768-200808000-00011#xpointer(id(R11-11))|11065405||ovftdb|SL00004337200610833211065405P64[Medline Link]|00005768-200808000-00011#xpointer(id(R12-11))|11065213||ovftdb|SL000054071990264265411065213P65[CrossRef]|00005768-200808000-00011#xpointer(id(R12-11))|11065405||ovftdb|SL000054071990264265411065405P65[Medline Link]|00005768-200808000-00011#xpointer(id(R13-11))|11065213||ovftdb|SL00003628200324147311065213P66[CrossRef]|00005768-200808000-00011#xpointer(id(R13-11))|11065405||ovftdb|SL00003628200324147311065405P66[Medline Link]|00005768-200808000-00011#xpointer(id(R14-11))|11065213||ovftdb|SL0000241219993323911065213P67[CrossRef]|00005768-200808000-00011#xpointer(id(R14-11))|11065405||ovftdb|SL0000241219993323911065405P67[Medline Link]|00005768-200808000-00011#xpointer(id(R17-11))|11065213||ovftdb|00003677-200210000-00008SL0000367720023018411065213P70[CrossRef]|00005768-200808000-00011#xpointer(id(R17-11))|11065404||ovftdb|00003677-200210000-00008SL0000367720023018411065404P70[Full Text]|00005768-200808000-00011#xpointer(id(R17-11))|11065405||ovftdb|00003677-200210000-00008SL0000367720023018411065405P70[Medline Link]|00005768-200808000-00011#xpointer(id(R19-11))|11065213||ovftdb|00003017-200112180-00031SL000030172001104306911065213P72[CrossRef]|00005768-200808000-00011#xpointer(id(R19-11))|11065404||ovftdb|00003017-200112180-00031SL000030172001104306911065404P72[Full Text]|00005768-200808000-00011#xpointer(id(R19-11))|11065405||ovftdb|00003017-200112180-00031SL000030172001104306911065405P72[Medline Link]|00005768-200808000-00011#xpointer(id(R20-11))|11065213||ovftdb|00006024-200011160-00003SL000060242000343144511065213P73[CrossRef]|00005768-200808000-00011#xpointer(id(R20-11))|11065404||ovftdb|00006024-200011160-00003SL000060242000343144511065404P73[Full Text]|00005768-200808000-00011#xpointer(id(R20-11))|11065405||ovftdb|00006024-200011160-00003SL000060242000343144511065405P73[Medline Link]|00005768-200808000-00011#xpointer(id(R22-11))|11065213||ovftdb|SL0000163019996192111065213P75[CrossRef]|00005768-200808000-00011#xpointer(id(R22-11))|11065405||ovftdb|SL0000163019996192111065405P75[Medline Link]|00005768-200808000-00011#xpointer(id(R25-11))|11065213||ovftdb|00002412-200707000-00016SL0000241220074144711065213P78[CrossRef]|00005768-200808000-00011#xpointer(id(R25-11))|11065404||ovftdb|00002412-200707000-00016SL0000241220074144711065404P78[Full Text]|00005768-200808000-00011#xpointer(id(R25-11))|11065405||ovftdb|00002412-200707000-00016SL0000241220074144711065405P78[Medline Link]|00005768-200808000-00011#xpointer(id(R27-11))|11065213||ovftdb|SL000055311992340104811065213P80[CrossRef]|00005768-200808000-00011#xpointer(id(R27-11))|11065405||ovftdb|SL000055311992340104811065405P80[Medline Link]|00005768-200808000-00011#xpointer(id(R28-11))|11065213||ovftdb|SL00004481199525126311065213P81[CrossRef]|00005768-200808000-00011#xpointer(id(R28-11))|11065405||ovftdb|SL00004481199525126311065405P81[Medline Link]|00005768-200808000-00011#xpointer(id(R29-11))|11065213||ovftdb|SL0000448119962842811065213P82[CrossRef]|00005768-200808000-00011#xpointer(id(R29-11))|11065405||ovftdb|SL0000448119962842811065405P82[Medline Link]|00005768-200808000-00011#xpointer(id(R30-11))|11065213||ovftdb|00003017-200307080-00024SL0000301720031085411065213P83[CrossRef]|00005768-200808000-00011#xpointer(id(R30-11))|11065404||ovftdb|00003017-200307080-00024SL0000301720031085411065404P83[Full Text]|00005768-200808000-00011#xpointer(id(R30-11))|11065405||ovftdb|00003017-200307080-00024SL0000301720031085411065405P83[Medline Link]|00005768-200808000-00011#xpointer(id(R31-11))|11065213||ovftdb|00060606-200207000-00006SL0006060620023127911065213P84[CrossRef]|00005768-200808000-00011#xpointer(id(R31-11))|11065404||ovftdb|00060606-200207000-00006SL0006060620023127911065404P84[Full Text]|00005768-200808000-00011#xpointer(id(R31-11))|11065405||ovftdb|00060606-200207000-00006SL0006060620023127911065405P84[Medline Link]|00005768-200808000-00011#xpointer(id(R32-11))|11065405||ovftdb|SL0000741619795626111065405P85[Medline Link]|00005768-200808000-00011#xpointer(id(R34-11))|11065213||ovftdb|SL00000406199412789811065213P87[CrossRef]|00005768-200808000-00011#xpointer(id(R34-11))|11065405||ovftdb|SL00000406199412789811065405P87[Medline Link]|00005768-200808000-00011#xpointer(id(R35-11))|11065213||ovftdb|SL00004481200443226011065213P88[CrossRef]|00005768-200808000-00011#xpointer(id(R35-11))|11065405||ovftdb|SL00004481200443226011065405P88[Medline Link]|00005768-200808000-00011#xpointer(id(R36-11))|11065213||ovftdb|00003628-200627090-00015SL00003628200627107911065213P89[CrossRef]|00005768-200808000-00011#xpointer(id(R36-11))|11065404||ovftdb|00003628-200627090-00015SL00003628200627107911065404P89[Full Text]|00005768-200808000-00011#xpointer(id(R36-11))|11065405||ovftdb|00003628-200627090-00015SL00003628200627107911065405P89[Medline Link]|00005768-200808000-00011#xpointer(id(R37-11))|11065213||ovftdb|SL0000674120044640411065213P90[CrossRef]|00005768-200808000-00011#xpointer(id(R37-11))|11065405||ovftdb|SL0000674120044640411065405P90[Medline Link]|00005768-200808000-00011#xpointer(id(R42-11))|11065213||ovftdb|SL00002953199199130611065213P95[CrossRef]|00005768-200808000-00011#xpointer(id(R42-11))|11065405||ovftdb|SL00002953199199130611065405P95[Medline Link]|00005768-200808000-00011#xpointer(id(R43-11))|11065213||ovftdb|SL00005531199234071211065213P96[CrossRef]|00005768-200808000-00011#xpointer(id(R43-11))|11065405||ovftdb|SL00005531199234071211065405P96[Medline Link]|00005768-200808000-00011#xpointer(id(R44-11))|11065213||ovftdb|00007256-199316020-00001SL000072561993167311065213P97[CrossRef]|00005768-200808000-00011#xpointer(id(R44-11))|11065404||ovftdb|00007256-199316020-00001SL000072561993167311065404P97[Full Text]|00005768-200808000-00011#xpointer(id(R44-11))|11065405||ovftdb|00007256-199316020-00001SL000072561993167311065405P97[Medline Link]|00005768-200808000-00011#xpointer(id(R47-11))|11065213||ovftdb|SL0000241219973126911065213P100[CrossRef]|00005768-200808000-00011#xpointer(id(R47-11))|11065405||ovftdb|SL0000241219973126911065405P100[Medline Link]|00005768-200808000-00011#xpointer(id(R49-11))|11065213||ovftdb|SL0000435520022348911065213P102[CrossRef]|00005768-200808000-00011#xpointer(id(R49-11))|11065405||ovftdb|SL0000435520022348911065405P102[Medline Link]|00005768-200808000-00011#xpointer(id(R51-11))|11065213||ovftdb|SL00006024198831812911065213P104[CrossRef]|00005768-200808000-00011#xpointer(id(R51-11))|11065405||ovftdb|SL00006024198831812911065405P104[Medline Link]|00005768-200808000-00011#xpointer(id(R52-11))|11065213||ovftdb|SL0000043919827287411065213P105[CrossRef]|00005768-200808000-00011#xpointer(id(R52-11))|11065405||ovftdb|SL0000043919827287411065405P105[Medline Link]|00005768-200808000-00011#xpointer(id(R53-11))|11065213||ovftdb|SL00005028199325131711065213P106[CrossRef]|00005768-200808000-00011#xpointer(id(R53-11))|11065405||ovftdb|SL00005028199325131711065405P106[Medline Link]|00005768-200808000-00011#xpointer(id(R54-11))|11065213||ovftdb|SL0000362819961790211065213P107[CrossRef]|00005768-200808000-00011#xpointer(id(R54-11))|11065405||ovftdb|SL0000362819961790211065405P107[Medline Link]|00005768-200808000-00011#xpointer(id(R55-11))|11065213||ovftdb|00005768-200006000-00005SL00005768200032106711065213P108[CrossRef]|00005768-200808000-00011#xpointer(id(R55-11))|11065404||ovftdb|00005768-200006000-00005SL00005768200032106711065404P108[Full Text]|00005768-200808000-00011#xpointer(id(R55-11))|11065405||ovftdb|00005768-200006000-00005SL00005768200032106711065405P108[Medline Link]|00005768-200808000-00011#xpointer(id(R56-11))|11065213||ovftdb|SL0000311120051087311065213P109[CrossRef]|00005768-200808000-00011#xpointer(id(R56-11))|11065405||ovftdb|SL0000311120051087311065405P109[Medline Link]|00005768-200808000-00011#xpointer(id(R57-11))|11065213||ovftdb|00003628-200728110-00029SL00003628200728139911065213P110[CrossRef]|00005768-200808000-00011#xpointer(id(R57-11))|11065404||ovftdb|00003628-200728110-00029SL00003628200728139911065404P110[Full Text]|00005768-200808000-00011#xpointer(id(R57-11))|11065405||ovftdb|00003628-200728110-00029SL00003628200728139911065405P110[Medline Link]|00005768-200808000-00011#xpointer(id(R60-11))|11065213||ovftdb|SL0000553120013572111065213P113[CrossRef]|00005768-200808000-00011#xpointer(id(R60-11))|11065405||ovftdb|SL0000553120013572111065405P113[Medline Link]|00005768-200808000-00011#xpointer(id(R61-11))|11065405||ovftdb|SL000037541961475611065405P114[Medline Link]14040353Clinical Significance of Cardiac Damage and Changes in Function after ExerciseWHYTE, GREGORY P.CLINICAL SCIENCES: Symposium: Exercise and the Heart840