The Athlete Grey Zone: Distinguishing Pathologic From Physiologic Left Ventricular Hypertrophy
The term "athlete's heart" is used to define the pattern of morphological, functional and electrical changes that result from intensive training including left ventricular hypertrophy (LVH). Elite athletes train and perform at levels that exceed most others' capabilities. As a result, physiologic adaptations related to training such as increased myocardial thickness may occur. The degree of hypertrophy associated with athletic physiologic adaptations can overlap with the pathologic hypertrophy of hypertrophic cardiomyopathy (HCM), leading to difficulty in distinguishing the two entities.
Athletic hypertrophy has previously been described as occurring in approximately 2% of athletes and varies by gender.1 Investigators in this field indicate that it takes approximately two years of intensive training of at least five hours per week to induce these adaptive changes, which are considered to be normal and are reversible with detraining.2-4 This is most notable in those athletes undergoing endurance training as compared to those involved in strength training. In their landmark study, Pellicia et al. demonstrated that some highly trained, elite athletes who developed LVH primarily increased septal thickness, which exceeded normal values (females up to 13 mm, and males up to 16 mm).5 An athlete with wall thickness between 12 and 16 mm represents the so called "grey zone" between the physiological adaptation of the athlete and pathologic expression of HCM. However, this data may be incomplete and not representative of all athletes. To that end, a recent evaluation of American football players suggests the previously published data from Pellicia et al. may not be accurate in this group of athletes.5 The findings, described at the ACC Annual Scietific Sessions in 2013, showed that LVH above 13 mm was present in nearly 10% of the American football athletes, a significant difference from the previously accepted upper limits of athletic wall thickness.
Distinguishing physiologic from pathologic hypertrophy for athletes can be difficult. A misdiagnosis can be devastating to the athlete with unnecessary interruption of training or elimination from competition. Conversely, an incorrect diagnosis of an athlete's heart may put a young life in harm's way and waive further risk stratification and evaluation of family members for this genetic condition. In this article, we discuss various techniques that can be utilized to help the clinician distinguish physiologic hypertrophy of the athlete and the pathologic hypertrophy of HCM.
History and Clinical Exam
The magnitude of LVH is largely determined by demographic factors including age, gender, ethnicity, size, and type of sporting discipline in which that athlete participates.6 Detailed knowledge of the training regimen undertaken by the individual is crucial in making the determination of athlete's heart versus HCM. For instance, adaptive LVH is most pronounced in those participating in sports with both isotonic and isometric components.7 In those with a family history of sudden death, HCM or a clinical exam with a resting/provocable systolic ejection murmur, a heightened suspicion and pointed discussion will be helpful.
ECG and Exercise Testing
Although many athletes show benign abnormalities on the ECG, the presence of changes such as T-wave inversions, pathological Q-waves and ST-segment depression especially in Caucasian athletes is concerning for pathological cardiac hypertrophy.8, 9
Cardiopulmonary exercise (CPX) testing is useful in differentiating athlete's heart from HCM. Many clinicians who see athletes often prefer a CPX to standard treadmill exercise testing (TMET). Standard testing may be helpful to identify the "true" athlete on the basis of exercise time and METs achieved; significantly higher values are expected in the athlete compared to the HCM patient. One advantage of CPX testing is the determination of oxygen consumption. One study found a VO2 max of <50 ml/kg/min is pathological and most suggestive of HCM.10 However, it should be noted that some HCM patients are able to exercise at a high level and, therefore, may be able to achieve VO2 exceeding this level.
Echocardiography is the mainstay of imaging for evaluation of the athletes. HCM is characterized by disparity between the magnitude of LVH and the left ventricular cavity size; LVH occurs at the expense of left ventricular cavity size. Most individuals with HCM have a small left ventricular cavity (<45 mm), while athletes with physiological LVH have concomitant enlargement of the left ventricular cavity. Some experts feel that left ventricular cavity size is the single most important discriminator between physiological LVH and HCM.7
In athlete's heart there is preservation of the ratio between wall thickness and end-diastolic diameter due to physiological increase in left ventricular volume. Typical values of left ventricular cavity size in athletes with LVH range between 55 and 65 mm, although up to 10% of athletes with LVH exhibit normal left ventricular cavity size.11,12 Individuals with HCM have LVH with pathognomonic diastolic dysfunction from increased muscle stiffness leading to impaired myocardial relaxation.13 Athletes rarely, if ever, have diastolic dysfunction. Typical features include a ratio of peak velocities of early (E) and late (A) phases of diastolic transmitral flow on pulsed-wave Doppler (without pseudo-normalization) that is significantly higher (super-normal) with athlete's heart compared to HCM. Athletes have a normal E wave deceleration time (between 100 and 220 milliseconds) and normal isovolumic relaxation time (<100 milliseconds). Additional cardiac mechanics include circumferential, radial and longitudinal motions, which are preserved in athletes and, in most cases, "super-normal." Assessment of longitudinal cardiac function with pulsed tissue Doppler in individuals with morphologically mild HCM, exhibit lower early diastolic velocities (E or e') compared with athletes. Echocardiographic hemodynamic assessment identifies normal filling pressures (E/e' <8) in athlete's heart as compared to HCM (E/e' > 15) and an e' of < 9 cm/s (sensitivity ~ 90%) favors HCM.13-15
Cardiac magnetic resonance (CMR) imaging evaluates both the right and left ventricle, coronary artery anomalies, valve disease, and aortic disease in a single modality, making it ideal for athlete evaluations. With regards to the grey zone, CMR allows for routine measurement with high reproducibility of the left ventricular thickness and accurate illustration and measurement of focal, apical and lateral wall hypertrophy. As a result, CMR is often superior to echocardiography for identifying the presence and severity of LVH.16 Post contrast imaging with CMR, referred to as late gadolinium enhancement (LGE), is able to detect myocardial fibrosis in most patients with HCM. Although the presence of LGE is not diagnostic for HCM, in those patients with mildly increased LV wall thickness, the presence of LGE would be suggestive of HCM rather than athletic adaptation.17
Endomyocardial biopsies have in general, no role. Although the presence of myocardial fiber disarray on biopsy is diagnostic of HCM, the yield and sensitivity is low due to the patchy nature of this pathological process and imparts a risk to the athlete.
Genetic testing currently has a limited role but does represent a potential emerging strategy for evaluation of the grey zone athlete. All genes responsible for the HCM phenotypes have not yet been identified, which leads to a positive test result only about 50% of the time.18-20 Therefore, a negative test result is common and does not exclude HCM. However, identification of a disease-causing sarcomere mutation would provide an answer to a grey zone level hypertrophied ventricle as pathologic.
Utilization of forced detraining may be employed as a last resort for individuals in whom the diagnosis is still unclear. Adaptive/physiologic cardiac hypertrophy unlike HCM should reverse (usually by 2-5 mm) after approximately three months of complete cessation of vigorous sporting activity.21, 22
Although we now know cardiovascular adaptation can produce increased ventricular chamber size (both right and left) as well as increased myocardial thickness, the primary purpose of this article was to discuss the so called "grey zone" as it relates to LVH. Adaptive cardiac hypertrophy in athletes can cause a dilemma in differentiating physiological from pathological hypertrophy such as seen with HCM. However, clinicians have several clinical tools and imaging modalities that will assist to successfully resolve the "grey zone" conundrum.
Findings That Suggest Pathologic LVH
- Pathologic Q-waves
- Peak VO2 max <50mL/kg/min
- LVH greater than 16 mm
- Presence of diastolic dysfunction
- Reduced longitudinal motion (Septal E prime velocity less than 9 cm/s)
- E/e' > 15
- Small left ventricular cavity diameter in end-diastole (<45 mm)
- Presence of late gadolinium enhancement (LGE) by CMR
- Maron BJ, Pelliccia A, Spirito P. Cardiac disease in young trained athletes. Insights into methods for distinguishing athlete's heart from structural heart disease, with particular emphasis on hypertrophic cardiomyopathy. Circulation 1995;91:1596-601.
- Maingourd Y, Bourges-Petit E, Tanguy C, et al. [Peripubertal longitudinal study by echocardiography of left heart development in a group of ice hockey players]. Arch Mal Coeur Vaiss 1990;83:371-5.
- Mesko D, Jurko A, Farsky S, Vrlik M. [Results of a 2-year study of echocardiographic parameters in juvenile athletes]. Cas Lek Cesk 1989;128:879-82.
- Obert P, Stecken F, Courteix D, Lecoq AM, Guenon P. Effect of long-term intensive endurance training on left ventricular structure and diastolic function in prepubertal children. Int J Sports Med 1998;19:149-54.
- Pelliccia A, Maron BJ, Spataro A, Proschan MA, Spirito P. The upper limit of physiologic cardiac hypertrophy in highly trained elite athletes. N Engl J Med 1991;324:295-301.
- Pluim BM, Zwinderman AH, van der Laarse A, van der Wall EE. The athlete's heart. A meta-analysis of cardiac structure and function. Circulation 2000;101:336-44.
- Rawlins J, Bhan A, Sharma S. Left ventricular hypertrophy in athletes. Eur J Echocardiogr 2009;10:350-356.
- Corrado D, Pelliccia A, Heidbuchel H, et al. Recommendations for interpretation of 12-lead electrocardiogram in the athlete. Eur Heart J 2010;31:243-59.
- Uberoi A, Stein R, Perez MV, et al. Interpretation of the electrocardiogram of young athletes. Circulation 2011;124:746-57.
- Sharma S, Elliott PM, Whyte G, et al. Utility of metabolic exercise testing in distinguishing hypertrophic cardiomyopathy from physiologic left ventricular hypertrophy in athletes. J Am Coll Cardiol 2000;36:864-70.
- Makan J, Sharma S, Firoozi S, et al. Physiological upper limits of ventricular cavity size in highly trained adolescent athletes. Heart 2005;91:495-99.
- Pelliccia A, Culasso F, Di Paolo FM, Maron BJ. Physiologic left ventricular cavity dilatation in elite athletes. Ann Intern Med 1999;130:23-31.
- 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.
- Ha JW, Ahn JA, Kim JM, et al. Abnormal longitudinal myocardial functional reserve assessed by exercise tissue Doppler echocardiography in patients with hypertrophic cardiomyopathy. J Am Soc Echocardiogr 2006;19:1314-9.
- Nagueh SF, Lakkis NM, Middleton KJ, et al. Doppler estimation of left ventricular filling pressures in patients with hypertrophic cardiomyopathy. Circulation 1999;99:254-61.
- Rickers C, Wilke NM, Jerosch-Herold M, et al. Utility of cardiac magnetic resonance imaging in the diagnosis of hypertrophic cardiomyopathy. Circulation 2005;112:855-61.
- Pelliccia A, Maron MS, Maron BJ. Assessment of left ventricular hypertrophy in a trained athlete: differential diagnosis of physiologic athlete's heart from pathologic hypertrophy. Prog Cardiovasc Dis 2012;54:387-96.
- Bos JM, Towbin JA, Ackerman MJ. Diagnostic, prognostic, and therapeutic implications of genetic testing for hypertrophic cardiomyopathy. J Am Coll Cardiol 2009;54:201-11.
- Wang L, Seidman JG, Seidman CE. Narrative review: harnessing molecular genetics for the diagnosis and management of hypertrophic cardiomyopathy. Ann Intern Med 2010;152:513-20, W181.
- Wordsworth S, Leal J, Blair E, et al. DNA testing for hypertrophic cardiomyopathy: a cost-effectiveness model. Eur Heart J 2010;31:926-35.
- Basavarajaiah S, Wilson M, Junagde S, et al. Physiological left ventricular hypertrophy or hypertrophic cardiomyopathy in an elite adolescent athlete: role of detraining in resolving the clinical dilemma. Br J Sports Med 2006;40:727-29.
- Maron BJ, Pelliccia A, Spataro A, Granata M. Reduction in left ventricular wall thickness after deconditioning in highly trained Olympic athletes. Br Heart J 1993;69:125-8.
Keywords: Athletes, Cardiomegaly, Hypertrophy, Myocardium, Heart Ventricles
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