Cardiac Disease in Young Trained Athletes
Insights Into Methods for Distinguishing Athlete’s Heart From Structural Heart Disease, With Particular Emphasis on Hypertrophic Cardiomyopathy
- Barry J. Maron, MD;
- Antonio Pelliccia, MD;
- Paolo Spirito, MD
- From the Cardiovascular Research Division, Minneapolis Heart Institute Foundation, Minneapolis, Minn; the Institute of Sports Science, Rome, Italy; and the Cardiology Division, Ente Ospedaliero Ospedali, Galliera, Genoa, Italy.
- Correspondence to Barry J. Maron, MD, Cardiovascular Research Division, Minneapolis Heart Institute Foundation, 920 E 28th St, Suite 40, Minneapolis, MN 55407.
Introduction
In young competitive athletes,1 the differential diagnosis between nonpathological changes in cardiac morphology associated with training (commonly referred to as “athlete’s heart”)2 3 4 and certain cardiac diseases with the potential for sudden death is an important and not uncommon clinical problem. Such crucial diagnostic distinctions most frequently involve hypertrophic cardiomyopathy (HCM), which is the most common cause of sudden death in young competitive athletes.5 6 7 Our awareness of this issue, as well as the parallel consideration of preparticipation athletic screening,8 9 has been heightened by several recent high-visibility catastrophies involving elite basketball players who died suddenly and unexpectedly from cardiovascular disease.10 11 12
The distinction between athlete’s heart and cardiac disease has particularly important implications, because identification of cardiovascular disease in an athlete may be the basis for disqualification from competition in an effort to minimize risk.13 By the same token, the improper diagnosis of cardiac disease in an athlete may lead to unnecessary withdrawal from athletics, thereby depriving that individual of the varied benefits of sport.
Consequently, interest in the application of noninvasive techniques that may aid in making such a diagnostic distinction and in planning subsequent clinical strategies has increased. Because this issue has not been examined in a comprehensive fashion, it is of value to assimilate the available data to develop a practical approach for the decision-making process directed toward the identification of cardiovascular disease in athletes.
Athlete’s Heart
While the entity of athlete’s heart has been recognized for over 100 years,2 3 4 only in the past two decades has the application of echocardiography and other noninvasive imaging techniques permitted definition with some precision of the alterations in cardiac dimensions associated with athletic conditioning.14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 Echocardiography has demonstrated that long-term athletic training leads to an increase in left ventricular mass due to increases in left ventricular diastolic cavity dimension, wall thickness, or both. These changes in cardiac morphology are relatively mild in absolute terms, and the differences between athlete and nonathlete populations are statistically significant but generally small.2 Furthermore, cardiac alterations associated with training differ somewhat depending on the particular sport in which the individual athlete participates.2 3 21 31 32 In particular, the changes in left ventricular wall thickness, cavity dimension, or both associated with long-term athletic training may be more striking in certain sports such as distance running, swimming, cycling, and rowing/canoeing. The differential diagnosis with cardiac disease is more likely to be raised in athletes training in such sports.
Cardiovascular Causes of Sudden Death
A variety of cardiovascular diseases have been identified as potential causes of sudden death in young competitive athletes (<35 years old).5 6 7 34 35 36 The vast majority of these deaths occur on the athletic field during severe exertion in the context of training or competition. Each of the responsible diseases is also known to cause sudden death in nonathletes. The most common cause of sudden death in young athletes appears to be HCM.5 6 7 34 Less common causes are a variety of congenital coronary artery anomalies, myocarditis, dilated cardiomyopathy, Marfan’s syndrome, and right ventricular dysplasia (in one series).35 36 Uncommon but reported causes of these athletic field catastrophies include sarcoid, mitral valve prolapse, aortic valve stenosis, atherosclerotic coronary artery disease, and QT-interval prolongation syndromes.
Differential Diagnosis Between Athlete’s Heart and Cardiovascular Disease
Dilated Cardiomyopathy
In an important minority of athletes, the increase in left ventricular diastolic cavity dimension that occurs with training overlaps with that characteristic of certain known pathological entities. For example, while left ventricular end-diastolic cavity dimension in athletes is usually in the range of 53 to 58 mm, in some individuals it may extend into what may be regarded as the pathological range of >58 mm and thereby resemble dilated cardiomyopathy.21 However, the absence of left ventricular systolic dysfunction is usually sufficient to distinguish this physiological ventricular enlargement induced by training from that due to dilated cardiomyopathy.
Myocarditis
Myocarditis, a disorder associated with a heterogeneous clinical profile, has recently been incriminated as the possible cause of some highly publicized deaths in athletes.10 37 While myocarditis usually has an infectious origin, it can also be a consequence of drug abuse.38 39 40 Sudden cardiac death may occur in its active or healed phases as a consequence of complex arrhythmias that develop in the setting of an unstable myocardial electrical substrate. In an athlete with myocarditis, left ventricular cavity enlargement may be due to the disease, to athletic training, or to a combination of these, but the differential diagnosis with athlete’s heart is usually resolved by the presence of clinically relevant and overt arrhythmias, cardiac symptoms such as syncope, presyncope and palpitations, or heart failure with systolic dysfunction. In some instances, the diagnosis may also be clarified by histological examination of myocardium obtained by endomyocardial biopsy.
Right Ventricular Dysplasia
Arrhythmogenic right ventricular dysplasia (or cardiomyopathy) is a heart muscle disorder of unknown cause that is characterized pathologically by fibrofatty replacement of the right ventricular myocardium.35 36 41 The clinical and phenotypic profile is variable but includes structural and functional abnormalities of the right ventricle, ventricular and supraventricular arrhythmias, familial occurrence, and the risk for sudden cardiac death.35 41 Indeed, it has been suggested that right ventricular dysplasia is an important cause of sudden death in the young, including competitive athletes, largely on the basis of reports from the northeastern (Veneto) region of Italy.35 36
Because highly trained athletes may demonstrate right ventricular enlargement33 and a variety of depolarization, repolarization, and conduction abnormalities on the ECG,3 4 42 the differential diagnosis between athlete’s heart and right ventricular dysplasia may arise. Noninvasive identification of right ventricular dysplasia by echocardiography43 may be difficult because of technical limitations in imaging right ventricular structure and assessing function in these patients and because the spectrum of the disease is broad and includes mild morphological forms with subtle manifestations.41 Magnetic resonance imaging, however, promises enhanced noninvasive diagnosis of this condition.44 The demonstration of right ventricular segmental or global dysfunction or substantial right ventricular cavity enlargement would support the diagnosis of right ventricular dysplasia; alternatively, thickening or enlargement of the left ventricle would be most consistent with athlete’s heart.2 3 4
Hypertrophic Cardiomyopathy
The greatest difficulty in distinguishing clinically between athlete’s heart and structural heart disease most frequently arises with respect to HCM, since many of the other cardiac disorders that cause sudden death in a young athletic population can be identified independently of any changes in cardiac morphology typically associated with training. The basic definition of HCM used here is that of a patient (or athlete) with evidence of a hypertrophied and nondilated left ventricle in the absence of another cardiac or systemic disease that could itself cause hypertrophy of the magnitude present in that individual.45
Wall Thickness
In the vast majority of competitive athletes, absolute left ventricular wall thickness is normal or only mildly increased (≤12 mm).2 3 4 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 In some athletes, however, the increase in left ventricular wall thickness may be more substantial, up to 16 mm, unavoidably raising the possibility of HCM.21 In patients with HCM, the increase in left ventricular wall thickness is usually marked; the average wall thickness reported in most echocardiographic studies of this disease is ≈20 mm,46 47 48 49 ranging to >50 mm.50 However, an important minority of patients with HCM show relatively mild left ventricular hypertrophy with wall thickness values in the range of ≈13 to 15 mm, and many of these patients are asymptomatic.47 49 51 52 53 Therefore, a diagnostic dilemma arises in those athletes who fall into this morphological “gray zone” between physiological hypertrophy and HCM2 (Fig 1⇓). While this distinction cannot be resolved with certainty in some of these athletes, careful analysis of several echocardiographic and clinical features permits this diagnostic differentiation in most.
Echocardiograms in parasternal long-axis view from an elite athlete (Olympic rower) (left) and a young asymptomatic patient with hypertrophic cardiomyopathy (HCM) (right). Magnitude of anterior ventricular septal (VS) hypertrophy is similar in each, demonstrating the morphological gray zone into which a highly trained athlete may fall and the diagnostic ambiguity that may ensue. Calibration dots are 1 cm apart. Left panel is reprinted by permission of the New England Journal of Medicine (1991;324:295-301).
Chart showing criteria used to distinguish hypertrophic cardiomyopathy (HCM) from athlete’s heart when the left ventricular (LV) wall thickness is within the shaded gray zone of overlap, consistent with both diagnoses. *Assumed to be the nonobstructive form of HCM in this discussion, since the presence of substantial mitral valve systolic anterior motion would confirm, per se, the diagnosis of HCM in an athlete. †May involve a variety of abnormalities, including heterogeneous distribution of left ventricular hypertrophy (LVH) in which asymmetry is prominent, and adjacent regions may be of greatly different thicknesses, with sharp transitions evident between segments; also, patterns in which the anterior ventricular septum is spared from the hypertrophic process and the region of predominant thickening may be in the posterior portion of septum or anterolateral or posterior free wall.47 55 ↓ indicates decreased; LA, left atrial.
In highly trained athletes, although the region of predominant left ventricular wall thickening always involves the anterior septum, the thicknesses of other segments of the wall are similar (with differences in the range of 1 to 2 mm). In patients with HCM, while the anterior portion of the ventricular septum is usually the region of maximal wall thickening, the pattern of hypertrophy is often heterogeneous,47 48 52 53 54 55 asymmetry is prominent, and areas other than the anterior septum may show the most marked thickening.55 In addition, contiguous portions of the left ventricle often show strikingly different wall thicknesses, and the transition between such areas is often sharp and abrupt. The diagnosis of HCM in asymptomatic athletes is frequently based solely on the echocardiographic assessment of the magnitude of hypertrophy and often on precise measurements of wall thickness in a single segment or region of the left ventricle. It should be emphasized that, in borderline cases, such circumstances present fertile ground for the overdiagnosis of HCM. This, in turn, creates considerable potential risk to the well-being of the athlete by possibly creating an unnecessary perception of heart disease.
Since a marked increase in left ventricular wall thickness often occurs during adolescence in patients with HCM,56 young athletes with HCM (<18 years old) may not demonstrate their maximum magnitude of hypertrophy until full physical maturation and development is achieved. Therefore, an athlete with HCM may initially be evaluated with echocardiography when the hypertrophy is still only mild and within the borderline range. The differential diagnosis with athlete’s heart may be difficult at that point in time. However, this uncertainty can be resolved by serial echocardiographic examinations, which, within months or years, may show more definite left ventricular wall thickening and confirm the diagnosis of HCM.
Cavity Dimension
An enlarged left ventricular end-diastolic cavity dimension (>55 mm) is present in more than one third of highly trained elite male athletes.21 32 Conversely, the diastolic cavity dimension is small, usually <45 mm, in most patients with HCM, and it is >55 mm only in those patients who evolve to the end-stage phase of the disease with progressive heart failure and systolic dysfunction.57 Therefore, in some instances, it is possible to distinguish the athlete’s heart from HCM solely on the basis of left ventricular diastolic cavity dimension. For example, a cavity >55 mm in an athlete with borderline wall thickness would constitute strong evidence against the presence of HCM; conversely, a cavity dimension <45 mm would be inconsistent with the athlete’s heart. However, in those athletes in whom left ventricular cavity size falls between these extremes, this variable alone will not resolve the differential diagnosis.
ECG
Because of the wide variety of ECG alterations present in both athletes without cardiovascular disease42 58 and patients with HCM, the 12-lead ECG is not particularly useful in distinguishing between these two entities. However, unusual and bizarre ECG patterns with strikingly increased voltages, prominent Q waves, or deep, negative T waves are most characteristic of HCM and represent evidence favoring this diagnosis.59 60 61
Doppler Transmitral Waveform
Abnormalities of left ventricular diastolic filling have been identified noninvasively with pulsed Doppler echocardiography or radionuclide angiography in many patients with a variety of cardiac diseases associated with left ventricular hypertrophy, such as systemic hypertension and HCM.62 63 64 65 66 Most patients with HCM, including those with relatively mild hypertrophy that could be confused with athlete’s heart, show abnormal Doppler diastolic indexes of left ventricular filling independently of whether symptoms or outflow obstructions are present.65 66 Typically, the early peak of transmitral flow-velocity (“E,” due to rapid filling) is decreased and deceleration time of the early peak is prolonged; the late peak (“A,” due to atrial contraction) is increased, inverting the normal E/A ratio. On the other hand, trained athletes have invariably demonstrated normal left ventricular filling patterns.21 66 67 68 69 70 71 72 Consequently, in a trained athlete suspected of having HCM, a distinctly abnormal Doppler pattern of transmitral flow-velocity strongly supports this diagnosis, while a normal Doppler pattern is compatible with either HCM or athlete’s heart.
Ultrasonic Myocardial Reflectivity (Integrated Backscatter Signal)
There has been interest in applying specialized ultrasound techniques to assessment of the acoustic properties of the myocardium for the purpose of resolving the differential diagnosis between athlete’s heart and HCM.73 74 Initial observations suggest that most asymptomatic (or mildly symptomatic) patients with HCM show increased intensity of the ultrasound signal from the septum and posterior free wall (including patients with mild and localized hypertrophy),73 while highly trained athletes with physiological hypertrophy show normal myocardial tissue reflectivity.74 One limitation in the use of the backscatter technique is its availability, which is at present confined to a few research institutions. In addition, it is not known whether differences in the backscatter signal identified by group comparisons can be used to distinguish athlete’s heart from cardiac disease in the individual subject.
Type of Sport Training
The specific nature of the athletic training itself has a major influence on the type and magnitude of the changes in left ventricular dimensions.20 21 22 23 24 25 26 27 28 29 30 31 32 33 For example, in a study of almost 1000 elite Italian athletes,21 only about 2% had a left ventricular wall thickness ≥13 mm (in the gray zone between physiological hypertrophy and HCM), and this subset was confined to rowing sports and cycling. Conversely, most other forms of training, including isometric (or power) sports such as weight-lifting or wrestling, were not associated with absolute increases in wall thickness beyond 12 mm.20 Therefore, in assessing whether an athlete with increased wall thickness has HCM, detailed knowledge of the training regimen is relevant. It is also possible that the outer limits of left ventricular wall thickness are different in trained athletes of various ethnic and racial origins, although this issue has not yet been resolved.
Sex
Sex differences with regard to alterations in cardiac dimensions and left ventricular mass have been identified in trained athletes.75 76 77 Preliminary findings indicate that highly trained female athletes rarely show left ventricular wall thicknesses that are within the aforementioned gray zone between athlete’s heart and HCM.75 In a recent report, none of 600 elite women athletes had left ventricular wall thickness in the range compatible with the diagnosis of HCM (≥13 mm).75 These observations suggest, therefore, that female athletes with “borderline” left ventricular wall thickness (in the presence of normal cavity size) are most likely to have HCM.
Regression of Left Ventricular Hypertrophy With Deconditioning
That increases in left ventricular cavity size or wall thickness are a physiological consequence of athletic training is shown by serial echocardiographic examinations demonstrating a decrease in cardiac dimensions and mass after athletic deconditioning.14 15 30 78 For example, elite athletes with left ventricular hypertrophy may show reduction in wall thickness (of about 2 to 5 mm) within 3 months of deconditioning.78 Identification of such changes in wall thickness with deconditioning, however, requires (1) compliance from highly motivated competitive athletes to interrupt training and (2) serial echocardiographic studies of optimal technical quality. Similar changes in left ventricular wall thickness with deconditioning are inconsistent with the presence of pathological hypertrophy and HCM.
Familial Transmission and Genetics
The most definitive evidence for the presence of HCM in an athlete with a substantial increase in wall thickness probably comes from the demonstration of the disease in a relative.44 79 80 Therefore, in those athletes in whom the distinction between HCM and athlete’s heart cannot be achieved definitively by other methods, one potential way of resolving this diagnostic uncertainty is the echocardiographic screening of family members. The absence of HCM in family members, however, does not exclude HCM, since the disease may be “sporadic” (ie, absent in relatives other than the index case), presumably as a result of de novo mutations.81
Recent advances in the understanding of the genetic alterations responsible for HCM raise the possibility of DNA diagnosis in athletes suspected of having this disease.79 80 81 82 The genetic abnormalities that cause HCM, however, are greatly heterogeneous. At present, mutations responsible for HCM have been identified in three genes located on chromosomes 14, 1, and 15; these genes encode the contractile proteins β-myosin heavy chain, cardiac troponin T, and α-tropomyosin, respectively.79 80 In addition, a fourth gene locus on chromosome 11 is known.83 Thus, mutations of at least four different genes can cause HCM. This substantial genetic heterogeneity of the disease makes it extremely difficult and time consuming at present to use the techniques of molecular biology for the purpose of resolving clinically the differential diagnosis between athlete’s heart and HCM.
Conclusions
In highly trained athletes with substantial left ventricular hypertrophy, it is of critical importance to clarify whether the increased left ventricular wall thickness represents the expression of the physiological adaptation of the heart to athletic training or a pathological condition such as HCM. While at present there is no single approach that will definitively resolve this question in all such athletes, several strategies are described here that alone or in combination offer a large measure of clarification in most instances for this often compelling diagnostic dilemma.
- Received August 2, 1994.
- Revision received September 26, 1994.
- Accepted October 30, 1994.
- Copyright © 1995 by American Heart Association
