The ‘Morganroth Hypothesis’ and left ventricular adaptations to endurance training

The major impetus in this field was provided by the first study to use echocardiography to image the athlete's heart.7 Morganroth and colleagues7 described an eccentric left ventricular (LV) hypertrophy in endurance athletes that reflected an increased LV internal dimension and mass, with minor changes in LV wall thickness. In a parallel group of resistance-trained athletes LV wall thickness and mass were increased but LV dimension was not, consequently the LV wall to chamber ratio was increased and Morganroth et al7 termed this concentric hypertrophy. A differential haemodynamic stimulus was proposed as the mechanism to explain this dichotomy and confirmatory cross-sectional8 and longitudinal evidence9 has prompted widespread adoption of these ideas.10 While most research has confirmed an eccentric LV hypertrophy in endurance athletes, the support for a concentric LV hypertrophy in resistance-trained athletes has been challenged by cross-sectional11 ,12 and longitudinal13 ,14 data sets.

The robust evidence supporting an eccentric LV hypertrophy in endurance athletes is exemplified by the outcome of two meta-analyses.15 ,16 The contention is that the LV adaptation to prolonged periods of training is important in the development of an enhanced cardio-respiratory capacity and endurance performance. Current knowledge of the upper limits of physiological adaptation of the LV is derived mainly from endurance athletes.17 ,18 Although more extreme LV dimensions have been reported in some endurance athletes,19 ,20 these data have not been replicated in more recent studies of similar athletes.21–23 Consequently, the current consensus is that the upper limit of physiological cardiac adaptation in endurance athletes is represented by an internal dimension of the LV of <65 mm and LV wall thickness of <14 mm (table 1). Concern for pathology and follow-up is needed when LV dimensions exceed these data.23

Cardiac dimensions in endurance athletes are subject to significant between-subject variability, but most subjects present with values below the normative limits reported in table 1. There are, however, a small number of endurance athletes who express cardiac dimensions above these upper normal limits and this overlaps with lower levels of disease penetrance in pathologies such as dilated cardiomyopathy  and hypertrophic cardiomyopathy (HCM). This overlap between physiology and pathology has been termed the ‘grey-zone’28 and reflects an area of diagnostic uncertainty. Approximately 80% of non-traumatic sudden deaths in young athletes are caused by inherited or congenital cardiac defects of which HCM is the most common pathology associated with sudden cardiac death.29 Superior athletic performance can co-exist with a hereditary cardiac disease; however, athlete deaths where HCM is implicated predominantly occur in intermittent power/speed sports such as soccer, American football and basketball.30 The observation of HCM in endurance athletes is rare,30 ,31 likely because HCM and an enhanced cardiac output sufficient to underpin endurance performance are thought to be incompatible.

Like cardiac morphology, there are some ECG patterns that have been reported in both the endurance athlete's heart and cardiac pathologies and these can overlap in the ‘grey zone’. Common ECG findings in the endurance athlete's heart, related to training, include sinus bradycardia, sinus arrhythmia, conduction delays, early repolarisation of the ST segment and isolated voltage criteria for LV hypertrophy (termed Group 1 ECG changes).32 ,33 A recent consensus statement33 also identified uncommon and usually training-unrelated ECG findings in athletes that include: T-wave inversion; ST-segment depression; pathological Q-waves; left atrial enlargement; left axis deviation/left anterior hemiblock; right axis deviation/left posterior hemiblock; right ventricular hypertrophy; ventricular pre-excitation; complete left or right bundle branch block; long-QT or short-QT interval; and Brugada-like early repolarisation (termed Group 2 ECG changes). These changes should be treated suspiciously for the presence of cardiac pathology and usually warrant further investigation. As an example, T-wave inversion ≥2 mm in two or more adjacent leads, especially in the inferior and lateral leads, is associated with risk of sudden cardiac death in cardiomyopathy (HCM or arrhythmogenic right ventricle cardiomyopathy (ARVC)), ischaemic heart disease, aortic valve disease, hypertension and LV non-compaction.33–37 These changes however may be a normal variant, especially anteriorly, with associated ST elevation preceding the T-wave inversion and when no other ECG abnormalities are present. Likewise T-wave inversions are more common in black athletes38 ,39 and the clinical relevance in these groups is not fully understood. Some common ECG changes may not apply to other ethnic groups and masters’ endurance athletes ([Cooper R, et al, unpublished data). For example, in asymptomatic endurance athletes >35 years of age with no documented history of coronary artery disease, the resting ECG has high false-negative and false-positive rates.40–42 Half of older athletes with normal coronary arteries on angiography have ECG abnormalities. The ECG as a screening tool in this older population is limited and the European Society of Cardiology recommends self-assessment using a validated questionnaire followed by exercise testing by a physician if the systematic coronary risk evaluation shows an increased risk for coronary events.43 Further research is required in this area.

Emerging evidence: the RV and left atria in the endurance athlete

Understanding RV adaptation to endurance exercise will inform the diagnostician in the process of differentiating physiological adaptation from inherited cardiomyopathies such as ARVC, which accounts for approximately 4% of cardiac sudden death in the athletic population.29 Similar to the LV, eccentric RV hypertrophy has been documented in endurance athletes.44 ,45 In support of cardiac magnetic resonance studies, recent echocardiographic studies have provided a more comprehensive evaluation of RV structure24–26 and some normative data are presented in table 1. D'Andrea et al26 and Oxborough et al25 demonstrated larger RV diameters at both the RV inflow and outflow in endurance athletes compared to published normal ranges, sedentary controls and strength-trained athletes.26 Furthermore, Oxborough et al25 demonstrated an increased RV:LV ratio, suggesting that the degree of remodelling maybe unequal in endurance athletes. This could be explained by a disproportionate wall stress being applied to the thin-walled RV.46

In view of ARVC being one of the main causes of cardiac sudden death in the athlete,29 these findings create a challenging diagnostic dilemma. Although the RV outflow tract in the endurance athlete is generally larger than in the normal healthy population, the RV inflow appears to be dilated to a greater degree.25 It is predominantly the RV outflow that is enlarged in ARVC and therefore the presence of a dilated RV inflow may be more representative of physiological conditioning in this setting.

It is important to consider RV function in the presence of significant RV remodelling, in that ARVC often results in an impairment to RV function.47–49 The development of strain imaging (figure 1) has provided scope for quantitative evaluation of regional and global RV function50 and Teske et al51 highlighted lower RV global strain values in elite endurance athletes, owing to a reduction in basal function. This finding has been reproduced in 40 endurance athletes at rest yet with augmented apical function24 that may suggest that global RV strain is likely to be a useful indicator of physiological adaptation.25 La Gerche et al24 demonstrated an enhanced contractile reserve of the basal RV segment during exercise and proposed that stress echocardiography may provide additional diagnostic value.

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Figure 1

Exemplar two-dimensional sector scan with myocardial speckle tracking of the right ventricle free wall and longitudinal strain data presented for basal, mid wall and apical wall segments. Speckle tracking determines deformation (strain) and the rate of deformation (strain rate) is specifically targeted wall segments that are determined by a semiautomated wall tracking system. In this figure it is useful to note the higher deformation values at the apex relative to the base.

In order to provide a sensible approach to the differentiation of ARVC from endurance athletic conditioning the presence of RV inflow dilatation, normal RV function during exercise (demonstrated using standard or quantitative echocardiography) and the lack of saccular outpouching in the RV outflow are consistent with physiological adaptation. Finally, the presence of a prominent RV moderator band has been evidenced in both ARVC48 and the endurance athlete49 and therefore should not be used as diagnostic criteria.

The left atrium (LA) of the endurance athlete has received even less attention than the RV. Oxborough et al25 observed a large indexed LA volume, with 88% of the 102 endurance athletes having values above the American Society of Echocardiography's normal range (figure 2 and table 1). This is also of importance when differentiating physiology from pathology and should be considered a normal finding in endurance athletes. It is difficult to fully ascertain the prognostic implications of LA remodeling; however, there is some evidence to suggest the endurance athlete has an increased risk of atrial fibrillation/flutter27 ,52 which correlates well with LA size.53 The LA is known to dilate in a non-uniform manner and therefore the use of LA volume and LA area is recommended over and above standard linear LA dimension54 and therefore may provide additional prognostic / diagnostic value.55 There is evidence of superior LA function in elite athletes when compared with patients with hypertensive LV hypertrophy;56 however, there are no data specifically in the endurance athlete population.

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Figure 2

Exemplar two-dimensional sector scan demonstrating the assessment of LA area (and consequently volume) using the Simpsons biplane method.

In summary, the heart of an endurance athlete is more than likely to demonstrate changes in morphology, function and electrical activity. This may place some endurance athletes in the diagnostic ‘grey-zone’ and it is crucial that an accurate determination of physiology or pathology is made. New research, with developing tools, is providing more insight into the phenotype of the athlete heart by detailing morphological adaptation in the RV and LA as well as documenting multiple facets of global and regional function. More data are required in heterogeneous groups of endurance athletes and in testing the utility of new imaging tools in helping diagnostic decision making.

(Ultra)Endurance exercise and cardiac function

During (ultra)endurance exercise, the total cardiac work is considerable and the heart must also cope with an elevation in core temperature, increased levels of catecholamines, increased mechanical work, altered pH and exposure to reactive oxygen species.57 Whether the heart can maintain performance in the face of such challenges has been the focus of recent debate. Since Saltin and Stenburg58 suggested that prolonged exercise could impair intrinsic cardiac contractile function, a number of studies have addressed the phenomenon of ‘exercise-induced cardiac fatigue’. In an attempt to provide consensus our group59–61 and others62 have reviewed the literature and Middleton et al59 performed a meta-analysis, collating data related to the effect of prolonged exercise on ejection fraction (global LV contractility) and the ratio of early to atrial peak diastolic filling velocities (global LV diastolic filling). A significant overall effect of exercise was noted for both parameters. The post-exercise reduction in ejection fraction was small (c.2%), was mediated by increasing exercise duration and poor training status and was related to changes in ventricular dimension (an index of preload). This latter point suggests that the reduction may be attributed, in part, to altered cardiac loading and not intrinsic cardiac function per se. The post-exercise decline in diastolic filling was more consistent between studies and was independent of loading and heart rate, suggesting a direct effect of exercise upon lusitropic function.

Ongoing developments with non-invasive imaging (tissue-Doppler imaging, strain/strain rate assessment), has extended our knowledge in this area. For example, speckle-tracking assessment of myocardial deformation has allowed strain and strain rate to be assessed in longitudinal, radial and circumferential planes and at basal, mid- and apical wall levels of the LV and in the longitudinal plane for the RV and LA. Using these approaches recent work has described a negative effect of prolonged exercise on RV function2 ,63 ,64 and LA function.65 Recent work by La Gerche et al64 suggests that exercise-induced changes in function may occur in the RV but not the LV. A postexercise drop in RV function was linked to cardiac biomarker appearance and increased race duration. While RV ejection fraction had returned to baseline one week after exercise, the link between a lower RV ejection fraction and chronic structural changes (evidence of cardiac fibrosis) would suggest that the clinical implications are worthy of ongoing study.

The determination of mechanism(s) underpinning changes in cardiac function following prolonged exercise is challenging,66 especially when dealing with human subjects using non-invasive imaging techniques. Although altered loading and heart rate may account for a proportion of the change in cardiac function, there is some evidence that supports other mechanisms. A downregulation of β-adrenoreceptors, related to reduced contractile state, has been shown previously in humans,67 ,68 although there are conflicting data in an animal model.69 Recently, Chan-Dewar and colleagues70 ,71 reported an increase in the electromechanical delay in the heart after prolonged exercise that was related to a decline in peak systolic tissue velocity. This suggests that the site of cardiac fatigue is beyond the electrical activation process and thus intrinsic to the myocytes. Whether this reflects changes in energy metabolism (substrate availability) or alterations in calcium handling cannot be deduced from human studies at this point in time. Another mechanism, which has received much attention, is a direct link between cardiomyocyte damage and reduced function. Data related to this specific theory are presented in the next subsection.

The concept of exercise-induced cardiac fatigue remains controversial and the clinical relevance of postexercise changes in cardiac function is not fully evaluated. Most descriptive data detail a rapid recovery of LV and/or RV dysfunction.60 There are, however, occasional reports of more persistent changes in function.2 ,72 La Gerche et al2 observed a postexercise reduction in RV tissue velocities that remained depressed at 1 week in one athlete, while Neilan et al72 reported reduced diastolic function 3–4 weeks following completion of the Boston Marathon. Further, a suggested link between increased RV end-systolic wall stress with exercise, RV dysfunction, RV remodelling and clinically relevant RV arrhythmias, in some endurance athletes,73 ,74 requires further study.

(Ultra)Endurance exercise and cardiac biomarker release

The potential that prolonged exercise can induce cardiomyocyte damage, which may underpin changes in heart function, has received significant attention recently.4 ,75 Multiple studies have reported significant elevations in cardiac troponin I or T (cTnI, cTnT), which are highly cardio-specific markers of cellular damage.4 These data have been reviewed4 ,76 and subjected to meta-analysis.77 In this meta-analysis, the overall event rate (positive serum sample for cTnT after prolonged exercise) was 47%. Continuing studies78 ,79 have attempted to attribute cTn release following prolonged activity to exercise characteristics (eg, duration or intensity) or subject-related parameters (eg, age or training status). To date, these data lack consistency and generally explains only a small proportion of the variance in data. Individual studies generally assess a single blood draw postexercise. We caution against this limited analysis as this will likely underestimate the true rate of cTn appearance during or following ultraendurance events. A unique laboratory-based marathon with blood draws every 30 min during the race and at frequent intervals during recovery observed elevated cTn in all runners.80

The clinical relevance of cTn release with exercise, and whether an elevated cTn explains changes in LV and RV function, is controversial. Following exercise the concentrations of cTn released are typically very small with very rapid appearance81 and removal. This is in contrast to cTn kinetics following myocardial infarction.4 Exercise is possibly the only documented cause of cTn release that is not associated with adverse clinical outcome. This has led to the hypothesis that an elevation in cTn is part of a normal physiological response to exercise4 and does not represent irreversible cell death. The mechanism(s) by which cTn moves from the cardiomyocytes to the intravascular space, during and after exercise, are not known. It is possible that cTn ‘leaks’ from the small fraction of unbound cTn contained in the cytosol. As the physiological environment (pH, temperature, oxidative and mechanical stress) during exercise changes, cardiomyocyte membrane permeability may also increase allowing cTn to move out of the cell. While most authors who have simultaneously assessed postexercise cardiac function and cTn release report no direct association,4 others have used correlational analysis to link the appearance of cTn to the reductions in cardiac function, notably in the RV.2 ,64

In summary, there is now convincing evidence that the performance of (ultra)endurance exercise can result in a small but temporary reduction in LV and RV function. At the same time, but likely due to different mechanisms, there is a release of cTn into the blood stream. It is likely that in most people these events are a normal, potentially adaptive, process associated with the ‘work’ of prolonged exercise. Further study is required to determine if the RV is more susceptible to ‘cardiac fatigue’ with prolonged exercise, whether these changes are associated with tissue damage and what the long-term consequences of such mal-adaptation might be.