Cardiac enlargement in trained athletes has long been recognized. Knowledge gained from the early tools of physical examination, chest radiography, and 12-lead electrocardiography has since been augmented by the development of echocardiography and cardiac MRI. These imaging modalities have led to improved characterization of the cardiac structural and functional adaptations to exercise training (i.e. ‘athlete's heart’). Left ventricular hypertrophy (LVH), an increase in left ventricle (LV) mass, is a well-recognized component of exercise-induced cardiac remodeling (EICR), and the form of LVH varies with sport type and primary hemodynamic load of exercise training . LVH also accompanies numerous cardiovascular diseases, most notably hypertrophic cardiomyopathy (HCM), the leading cause of exercise-related sudden cardiac death in athletes . Although the degree of physiological LVH is typically mild in trained athletes, in some LVH may involve wall thickening that is substantial enough to prompt concern for HCM. Differentiation between physiologic EICR and disease in such ambiguous cases of ‘gray-zone’ LVH is of critical importance, because athletes with HCM are at increased risk of sudden death and restricted from sport participation . This article will provide an overview of EICR (athlete's heart), delineate the imaging strategies currently available to evaluate ‘gray-zone’ LVH, and explore novel imaging tools that may improve clarity in distinguishing EICR from pathologic LVH.
OVERVIEW: EXERCISE-INDUCED CARDIAC REMODELING
Understanding the cardiac adaptations to exercise first requires a basic understanding of the hemodynamic changes that occur during exercise. Although considerable overlap exists, exercise activity can be broadly separated into two major physiologic forms with defining hemodynamic characteristics . Isotonic or endurance exercise involves sustained increases in the body's demand for oxygen. The increased demand for oxygen, in the healthy human, is met by increased cardiac output (CO). CO may increase by five-fold during a maximal exercise effort, and when maintained for long periods, as in endurance exercise training, results in a primary volume load on the heart, including all four cardiac chambers. This form of exercise is predominant in activities including long distance running, swimming, cycling, and rowing. An increase in LV diastolic chamber size is the principal cardiac adaptation to endurance exercise training. This may be accompanied by a balanced increase in LV mass with resultant eccentric LVH and typically normal wall thickness.
In contrast, isometric or strength-based exercise consists of intermittent, short but intense contractions of muscle mass. This leads to transient increases in peripheral vascular resistance and resultant systolic hypertension. CO is normal or only slightly elevated. Isometric exercise places a primary pressure load on the heart. The activities of weightlifters, American-style football players (particularly linemen), and track and field throwers typify this form of exercise. A mild increase in LV wall thickness is the typical cardiac adaptation to strength exercise, resulting in concentric exercise-induced LVH. This form of EICR can be the ‘mimicker’ of HCM.
LIMITS OF THE ‘ATHLETE'S HEART’: THE THICKENED LEFT VENTRICLE
Thickening of the LV, without associated LV chamber dilation, occurs infrequently in trained athletes. Wall thickness ‘cut-off’ values may be helpful in distinguishing athlete's heart from disease (HCM), as LV wall thickness >15 mm should be considered pathologic until proven otherwise. Additionally, the pattern of LVH may be useful. LVH in strength-trained athletes is typically symmetric, and the presence of asymmetry typically suggests HCM, although this notion has been questioned in a recent study of healthy young athletic men .
Pelliccia et al.  evaluated LV wall thickness on echocardiography in 947 elite Italian athletes. Among these athletes, who were exclusively Caucasian, a small percentage had LV wall thicknesses of ≥13 mm (1.7%). A similarly low prevalence of LV wall thickness >12 mm has been reported in elite junior athletes (0.4%)  and in 3500 elite British athletes (1.5%) . Importantly, in these studies, elevated wall thickness was associated with LV cavity dilation. In our group's study of nearly 500 healthy university athletes, no participants had wall thickness of >14 mm . In summary, LV wall thickness in excess of 13 mm is a rare finding in healthy athletes, although it can be seen in a small number of healthy, highly trained individuals. This finding is more common in athletes with relatively large body size and those of Afro-Caribbean descent .
The degree of LVH in an athlete is governed by numerous factors. In addition to sport type and training intensity, age (older), sex (male), and body size (larger) have all been associated with thicker LV walls [11–13]. The importance of ethnicity in influencing the morphological manifestations of EICR has also been recognized [8,10]. Additionally, the duration of exercise training is becoming appreciated as a determinant of EICR and is an area of active investigation [14▪].
GRAY-ZONE HYPERTROPHY: DISEASE VERSUS PHYSIOLOGY
As outlined above, a small number of healthy trained athletes demonstrate hypertrophy with LV wall thickness in the 13–15 mm range, which overlaps with that seen in phenotypically mild HCM and represents a ‘gray zone’ in which it is difficult to distinguish physiological and pathological hypertrophy. The diagnostic dilemma of gray-zone hypertrophy is significant, given the risk of sudden cardiac death with exercise in HCM and the burden of lifelong restriction from competitive sports in patients with HCM. Figure 1 highlights the elements of the diagnostic ‘toolkit’ available to clinicians in the evaluation of gray-zone hypertrophy. The imaging tools used in this evaluation are highlighted below.
ECHOCARDIOGRAPHY: CONVENTIONAL MEASUREMENTS OF STRUCTURE AND FUNCTION
As noted above, LV wall thickness >15 mm is rare even in highly trained athletes, and typically wall thickening in athletes is associated with LV chamber dilation. A recent study evaluated various simple echocardiographic and clinical variables in distinguishing the cause of gray-zone LVH in a cohort of athletes and patients with HCM. Athletes had larger LV cavities (60 ± 3 vs. 45 ± 5 mm, P < 0.001) than HCM patients, and LV cavity size < 54 mm best distinguished HCM from athlete's heart with the highest sensitivity and specificity (100% in this small population, n = 53) [15▪▪].
Diastolic function as assessed by echocardiography may also aid in the differentiation of HCM from athlete's heart. Traditional Doppler metrics of diastolic function, including transmitral filling and pulmonary vein inflow, are typically normal in athletes with LVH  and abnormal in patients with HCM, independent of whether symptoms or outflow obstruction is present . Later studies have used tissue Doppler echocardiography to assess diastolic function, which has the advantage of being less load-dependent than traditional Doppler measures, and have found similar impairment in diastolic filling in HCM patients as compared with trained athletes . In the recent study of athletes and HCM patients, athletes showed higher E′ velocity by tissue Doppler imaging than patients with HCM (12.5 ± 1.9 vs. 9.3 ± 2.3 cm/s, P < 0.001), with values <11.5 cm/s yielding sensitivity of 81% and specificity of 61% for the diagnosis of HCM (P < 0.001) [15▪▪].
However, these studies of diastolic function have not focused on strength-trained athletes, the group most likely to develop the concentric geometry of LVH that may be the most difficult to distinguish from HCM. A more recent longitudinal study of male American-style football players with concentric LVH revealed relative impairment of LV diastolic function with training as assessed by tissue Doppler echocardiography . This finding may potentially be explained by resting hypertension in this population of athletes , and whether this form of athlete's heart may represent a precursor to hypertensive heart disease and be maladaptive is controversial and requires further study. Study of diastolic function in primary strength-based athletes is therefore an area of active investigation, both to more reliably aid in the distinction of physiologic LVH and HCM and also to determine the prognostic significance, if any, of exercise-induced LVH in strength-based athletes.
It will be unlikely that a single echocardiographic parameter will be able to distinguish EICR and HCM in gray-zone cases. An integrated approach with echocardiography, including both structural and functional measures, combined with other testing (Fig. 1) may be useful. A recent study evaluated the efficacy of such an approach and found that in a small cohort of healthy athletes and established HCM patients with similar degrees of ‘gray-zone’ LVH, a point score based on combination of echocardiographic LV dimensions, diastolic function, and serum biomarkers could predict underlying cardiomyopathy . This type of approach needs to be validated in larger populations, and it remains likely that echocardiographic techniques will need to be combined with other testing modalities in gray-zone situations. Additionally, novel echocardiographic techniques to assess myocardial mechanics, as described below, may have potential for providing further clarity in this clinically challenging situation.
NOVEL ECHOCARDIOGRAPHIC TECHNIQUES: MYOCARDIAL MECHANICAL IMAGING
Myocardial mechanical imaging as assessed by speckle tracking echocardiography has refined the assessment of both systolic and diastolic function in athlete's heart and HCM. Specifically, regional myocardial systolic deformation, or strain, has been assessed in these populations. Several studies have demonstrated that HCM patients have abnormally low strain and strain rate, which is associated with both the degree of hypertrophy and presence of myocardial fibrosis [22,23]. Longitudinal studies have demonstrated that endurance exercise training and the development of exercise-induced eccentric LVH is associated with overall augmentation in LV strain with regional heterogeneity . A recent comparative study using two-dimensional speckle tracking echocardiography for evaluation of strain in patients with HCM and athletes with LVH found that those with HCM had significantly lower regional and average global longitudinal strain (GLS) (average GLS −11.2 ± 4.2% vs. −17.8 ± 2.2%). Additionally, abnormal GLS has recently been shown to be an independent predictor of adverse outcomes in HCM patients [26▪]. Study of LV strain in primarily strength-based athletes and comparison with HCM patients is needed to evaluate whether it can help differentiate EICR from HCM in this group of athletes.
LV systolic rotation/twist and diastolic untwisting are increasingly recognized as an important component of LV function. Currently, there are discrepancies in the LV twist literature in athletes that have arisen from the comparison of cross-sectional and short-duration longitudinal studies. Specifically, several cross-sectional reports describe normal or reduced values of resting LV twist in endurance athlete groups such as cyclists  or soccer players , while short-duration longitudinal studies suggest that endurance training results in increased LV apical rotation and LV twist [29,30]. This apparent paradox is likely to be explained by accounting for the athletes’ ‘stage of training’, with cross-sectional studies having captured more ‘seasoned’ athletes at advanced levels of training (i.e. chronic adaptations) and the available longitudinal studies focused on younger athletes exposed to more acute adaptation. Further studies that engage individuals during both proposed periods of exercise exposure will be required to resolve this area of uncertainty.
LV diastolic untwisting is believed to serve as a key mechanism for early diastolic LV filling. In patients with HCM, particularly those with dynamic left ventricular outflow tract obstruction, untwisting has been shown to be delayed when compared with healthy nonathlete controls . More recently, LV untwisting has been directly compared in subjects with athlete's heart and HCM, and found to be significantly earlier (% untwist at mitral valve (MV) opening 51.3 ± 19.1 vs. 11.6 ± 10.4%) and faster (untwisting rate at time of MV opening −32.5 ± 13.0 vs. −10.6 ± 10.8 °/s) in athletes [32▪▪].
In sum, these provocative results suggest that the addition of advanced myocardial mechanical imaging to conventional echocardiographic measurements of structure and function may improve our ability to distinguish pathologic from physiologic gray-zone hypertrophy, although more work is needed before these parameters are used in routine clinical practice.
CARDIAC MAGNETIC RESONANCE IMAGING
Although the majority of existing data regarding the range of normal cardiac structure and function in athletes versus HCM patients are from echocardiographic studies, cardiac MRI also affords excellent and often superior visualization of the entire heart, including accurate quantification of ventricular mass and volume as well as identification of focal areas of hypertrophy, particularly when limited to the anterior free wall, posterior septum, and apex . As such, cardiac magnetic resonance (CMR) is increasingly employed in cases of suspected or diagnosed HCM. A recent study evaluated MRI measurements of LV mass and LV end-diastolic volume in patients with HCM, athletes, and healthy nonathletic controls, and found that HCM patients had a significantly lower LV mass: LV end-diastolic volume ratio than athletes (1.30 vs. 2.25, P < 0.05). This measure, incorporated into a model adjusting for age, sport participation, and sex, resulted in excellent prediction of HCM status in those subjects with borderline LVH .
CMR has also recently provided important insight into the range of asymmetrical wall thickening that might be expected in a normal healthy athletic population. A study using CMR in healthy young army recruits before and after intense exercise training revealed both a high prevalence of a maximal wall thickness >13 mm (23%) and an increased prevalence of asymmetrical wall thickening (defined on a segment basis as >13 mm and 1.5× thickness of opposing myocardial segment) from 2% to 10% with exercise training . The differences between prior echocardiographic studies and this data are likely in part due to the greater ability of CMR to accurately evaluate regional wall thickness in all myocardial segments, and further work will be necessary to define the degree of asymmetry, if any, that is useful to distinguish physiologic versus pathologic LVH on CMR.
Finally, contrast-enhanced CMR with late gadolinium enhancement (LGE) can detect myocardial fibrosis, which is present in a significant portion of patients with HCM, particularly in regions of hypertrophy or at the right ventricular hinge points within the ventricular septum. LGE has also been identified in long-time endurance athletes [35,36], and the degree of overlap between the amount and patterns of LGE in HCM patients and athletes has not yet been defined.
ROLE FOR DETRAINING
Cases of gray-zone hypertrophy may remain undifferentiated despite a comprehensive diagnostic approach, and in these instances, prescribed detraining and follow-up cardiac imaging to assess for LVH regression may be required. Maron et al.  documented regression of eccentric LVH among Olympic athletes over 6 to 34 weeks (mean 13 weeks). The largest detraining report to date studied 40 elite Italian male athletes with eccentric LVH (LV dimension = 61.2 ± 2.9 mm, LV wall thickness = 12.0 ± 1.3 mm), and found complete normalization of wall thickness but incomplete reduction in cavity dilation after 5.8 ± 3.6 years of detraining . The response of exercise-induced concentric LVH, which is more similar morphologically to HCM, to prescribed detraining has not been well studied. A recent small study of five strength-trained athletes with concentric LVH showed significant regression of LV mass and LV wall thickness during detraining . However, despite the improvement in LV structural parameters, there was persistent impairment of diastolic function as measured by lateral E′ velocity. Further investigation is needed to delineate the range of expected structural and functional changes in strength athletes undergoing prescribed detraining.
Cardiac structural and functional adaptation to exercise training, known as athlete's heart or exercise-induced cardiac remodeling, is believed to be an overall beneficial adaptation to exercise training. Different forms of exercise produce different types of EICR, with strength-based (isometric) exercises resulting in thickened LV walls. Wall thickness >15 mm and that occurring in an asymmetric pattern is most likely pathological as opposed to EICR. There are cases of ‘gray-zone’ LVH, typically 13–15 mm, in which it may be difficult to distinguish EICR from mild forms of HCM. An integrated clinical approach, with cardiac imaging (echocardiography and MRI) playing an essential role, is necessary to make this important distinction. Active study investigating myocardial mechanical properties is helping to provide further insight to more reliably distinguish EICR and HCM. The most pressing need for further study of EICR is in strength-based athletes, the group most likely to develop EICR that mimics HCM.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
1. Morganroth J, Maron BJ, Henry WL, et al. Comparative left ventricular dimensions in trained athletes. Ann Intern Med 1975; 82:521–524.
2. Maron BJ. Sudden death in young athletes. N Engl J Med 2003; 349:1064–1075.
3. Maron BJ, Olivotto I, Spirito P, et al. Epidemiology of hypertrophic cardiomyopathy-related death: revisited in a large nonreferral-based patient population. Circulation 2000; 102:858–864.
4. Maron BJ, Douglas PS, Graham TP, et al. Task Force 1: preparticipation screening and diagnosis of cardiovascular disease in athletes. J Am Coll Cardiol 2005; 45:1322–1326.
5. Lee PT, Dweck MR, Prasher S, et al. Left ventricular wall thickness and the presence of asymmetric hypertrophy in healthy young army recruits: data from the LARGE heart study. Circ Cardiovasc Imaging 2013; 6:262–267.
6. Pelliccia A, Maron BJ, Spataro A, et al. The upper limit of physiologic cardiac hypertrophy in highly trained elite athletes. N Engl J Med 1991; 324:295–301.
7. Sharma S, Maron BJ, Whyte G, et al. Physiologic limits of left ventricular hypertrophy in elite junior athletes: relevance to differential diagnosis of athlete's heart
and hypertrophic cardiomyopathy. J Am Coll Cardiol 2002; 408:1431–1436.
8. Basavarajaiah S, Wilson M, Whyte G, et al. Prevalence of hypertrophic cardiomyopathy in highly trained athletes: relevance to preparticipation screening. J Am Coll Cardiol 2008; 51:1033–1039.
9. Weiner RB, Wang F, Hutter AM, et al. The feasibility, diagnostic yield, and learning curve of portable echocardiography for out-of-hospital cardiovascular disease screening. J Am Soc Echocardiogr 2012; 25:568–575.
10. Rawlins J, Carre F, Kervio G, et al. Ethnic differences in physiological cardiac adaptation to intense physical exercise
in highly trained female athletes. Circulation 2010; 121:1078–1085.
11. Pelliccia A, Maron BJ, Culasso F, et al. Athlete's heart
in women. Echocardiographic characterization of highly trained elite female athletes. JAMA 1996; 276:211–215.
12. Pluim BM, Zwinderman AH, van der Laarse A, et al. The athlete's heart
. A meta-analysis of cardiac structure and function. Circulation 2000; 101:336–344.
13. Sharma S. Athlete's heart
– effect of age, sex, ethnicity and sporting discipline. Exp Physiol 2003; 88:665–669.
14▪. Weiner RB, Baggish AL. Acute versus chronic exercise
-induced left ventricular remodeling
. Exp Rev Cardiovasc Ther 2014; 12:1243–1246.
This article summarizes the many determinants of exercise-induced cardiac remodeling, with a focus on the concept that prior exercise exposure and the stage of exercise training are increasingly recognized factors.
15▪▪. Caselli S, Maron MS, Urbano-Moral JA, et al. Differentiating left ventricular hypertrophy in athletes from that in patients with hypertrophic cardiomyopathy. Am J Cardiol 2014; 114:1383–1389.
This important study aimed to improve the identification of HCM in young athletes with LV wall thickness 13–15 mm. Left ventricular cavity size was the most reliable criterion to establish the diagnosis of HCM, with a cut-off value of <54 mm useful for differentiation from athlete's heart. Other criteria, including LV diastolic dysfunction, absence of T-wave inversion on electrocardiography, and negative family history, further aided in the differential diagnosis.
16. Lewis JF, Spirito P, Pelliccia A, et al. Usefulness of Doppler echocardiographic assessment of diastolic filling in distinguishing ‘athlete's heart
’ from hypertrophic cardiomyopathy. Br Heart J 1992; 68:296–300.
17. Maron BJ, Spirito P, Green KJ, et al. Noninvasive assessment of left ventricular diastolic function by pulsed Doppler echocardiography in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1987; 10:733–742.
18. Vinereanu D, Florescu N, Sculthorpe N, et al. Differentiation between pathologic and physiologic left ventricular hypertrophy by tissue Doppler assessment of long-axis function in patients with hypertrophic cardiomyopathy or systemic hypertension and in athletes. Am J Cardiol 2001; 88:53–58.
19. Baggish AL, Wang F, Weiner RB, et al. Training-specific changes in cardiac structure and function: a prospective and longitudinal assessment of competitive athletes. J Appl Physiol 2008; 104:1121–1128.
20. Weiner RB, Wang F, Isaacs SK, et al. Blood pressure and left ventricular hypertrophy during American style football participation. Circulation 2013; 128:524–531.
21. Pagourelias ED, Efthimiadis GK, Kouidi E, et al. Efficacy of various ‘classic’ echocardiographic and laboratory indices in distinguishing the ‘gray zone’ between athlete's heart
and hypertrophic cardiomyopathy: a pilot study. Echocardiography 2013; 30:131–139.
22. Ganame J, Mertens L, Eidem BW, et al. Regional myocardial deformation in children with hypertrophic cardiomyopathy: morphological and clinical correlations. Eur Heart J 2007; 28:2886–2894.
23. Popović ZB, Kwon DH, Mishra M, et al. Association between regional ventricular function and myocardial fibrosis in hypertrophic cardiomyopathy assessed by speckle tracking echocardiography and delayed hyperenhancement magnetic resonance imaging. J Am Soc Echocardiogr 2008; 21:1299–1305.
24. Baggish AL, Yared K, Wang F, et al. The impact of endurance exercise
training on left ventricular systolic mechanics. Am J Physiol Heart Circ Physiol 2008; 295:H1109–H1116.
25. Afonso L, Kondur A, Simegn M, et al. Two-dimensional strain profiles in patients with physiological and pathological hypertrophy and preserved left ventricular systolic function: a comparative analyses. BMJ Open 2012; 2:4.
26▪. Hartlage GR, Kim JH, Strickland PT, et al. The prognostic value of standardized reference values for speckle-tracking global longitudinal strain in hypertrophic cardiomyopathy. Int J Cardiovasc Imaging 2015; 31:557–565.
Using recently published reference values for GLS, this study aimed to evaluate the prognostic value of GLS in HCM patients. Abnormal GLS was found to be an independent predictor of adverse outcomes in HCM patients.
27. Nottin S, Doucende G, Schuster-Beck I, et al. Alteration in left ventricular normal and shear strains evaluated by 2D-strain echocardiography in the athlete's heart
. J Physiol 2008; 586:4721–4733.
28. Zocalo Y, Bia D, Armentano RL, et al. Assessment of training-dependent changes in the left ventricle torsion dynamics of professional soccer players using speckle-tracking echocardiography. Conf Proc IEEE Eng Med Biol Soc 2007; 2007:2709–2712.
29. Weiner RB, Hutter AM Jr, Wang F, et al. The impact of endurance exercise
training on left ventricular torsion. JACC Cardiovasc Imaging 2010; 3:1001–1009.
30. Aksakal E, Kurt M, Oztürk ME, et al. The effect of incremental endurance exercise
training on left ventricular mechanics: a prospective observational deformation imaging study. Anadolu Kardiyol Derg 2013; 13:432–438.
31. Wang J, Buergler JM, Veerasamy K, et al. Delayed untwisting: the mechanistic link between dynamic obstruction and exercise
tolerance in patients with hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 2009; 54:1326–1334.
32▪▪. Kovács A, Apor A, Nagy A, et al. Left ventricular untwisting in athlete's heart
: key role in early diastolic filling? Int J Sports Med 2014; 35:259–264.
This study investigated diastolic function and untwisting dynamics in different forms of LVH (athlete's heart and HCM). Unlike HCM, athlete's heart was characterized by increased untwisting and untwisting rate, which aids diastolic function. Evaluation of untwisting dynamics may therefore help to distinguish physiological and pathological hypertrophy.
33. Maron MS, Maron BJ, Harrigan C, et al. Hypertrophic cardiomyopathy phenotype revisited after 50 years with cardiovascular magnetic resonance. J Am Coll Cardiol 2009; 54:220–228.
34. Luijkx T, Cramer MJ, Buckens CF, et al. Unravelling the grey zone: cardiac MRI volume to wall mass ratio to differentiate hypertrophic cardiomyopathy and the athlete's heart
. Br J Sports Med 2013; [Epub ahead of print].
35. 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.
36. Wilson M, O’Hanlon R, Prasad S, et al. Diverse patterns of myocardial fibrosis in lifelong, veteran endurance athletes. J Appl Physiol 2011; 110:1622–1626.
37. Maron BJ, Pelliccia A, Spataro A, et al. Reduction in left ventricular wall thickness after deconditioning in highly trained Olympic athletes. Br Heart J 1993; 69:125–128.
38. Pelliccia A, Maron BJ, De Luca R, et al. Remodeling of left ventricular hypertrophy in elite athletes after long-term deconditioning. Circulation 2002; 105:944–949.
39. Weiner RB, Wang F, Berkstresser B, et al. Regression of ‘gray zone’ exercise
-induced concentric left ventricular hypertrophy during prescribed detraining. J Am Coll Cardiol 2012; 59:1992–1994.