Skip main navigation

Clinical Profile of Athletes With Hypertrophic Cardiomyopathy

Originally publishedhttps://doi.org/10.1161/CIRCIMAGING.114.003454Circulation: Cardiovascular Imaging. 2015;8

Abstract

Background—

The phenotype of individuals with hypertrophic cardiomyopathy (HCM) who exercise regularly is unknown. This study characterized the clinical profile of young athletes with HCM.

Methods and Results—

The electrical, structural, and functional cardiac parameters from 106 young (14–35 years) athletes with HCM were compared with 101 sedentary HCM patients. A subset of athletes with HCM exhibiting morphologically mild (13–16 mm), concentric disease was compared with 55 healthy athletes with mild physiological left ventricular hypertrophy (LVH). Most athletes with HCM (96%) exhibited T-wave inversion and had milder LVH (15.8±3.4 mm versus 19.7±6.5 mm, P<0.001), larger left ventricular cavity dimensions (47.8±6.0 mm versus 44.3±7.7 mm, P<0.001), and superior indices of diastolic function (average E/E′ 7.9±2.4 versus 10.7±3.9, P<0.001) compared with sedentary HCM patients. In athletes with HCM, LVH was frequently (36%) confined to the apex and only 15 individuals (14%) exhibited mild concentric LVH mimicking physiological LVH. In these 15 athletes, conventional structural and functional cardiac parameters showed modest sensitivity and specificity for differentiating HCM from physiological LVH: 13% had a left ventricular cavity >54 mm, 87% had a left atrium ≤40, and 100% had an E/E′ <12.

Conclusions—

Athletes with HCM exhibit less LVH, larger left ventricular cavities, and normal indices of diastolic function compared with sedentary patients. Only a minority of athletes with HCM constitute the conventional gray zone of mild, concentric LVH. In this minority, conventional echocardiographic parameters alone are insufficient to differentiate HCM from physiological LVH and should be complemented by additional structural and functional assessments to minimize the risk of false reassurance.

Introduction

Hypertrophic cardiomyopathy (HCM) is a heterogeneous condition with highly variable phenotypic expression and is the leading cause of sudden cardiac death in young athletes worldwide.1 The clinical profile of athletes with HCM capable of competing in sporting activities at an extraordinarily high level has not been characterized. Traditional methods for differentiating physiological left ventricular hypertrophy (athlete’s heart) from HCM have relied on parameters derived from sedentary HCM patients and healthy athletes.25 Anecdotal evidence suggests that such algorithms2 may not be directly applicable to athletes with HCM.68

See Clinical Perspective

This study sought to characterize the clinical profile of young athletes with HCM diagnosed during preparticipation cardiovascular evaluation or in the context of family screening. The results were compared with young sedentary HCM patients to determine differences in disease phenotype between individuals with HCM who exercise regularly and those who are sedentary. The results from a small subset of athletes with HCM revealing mild (13–16 mm) concentric left ventricular hypertrophy (LVH) were also compared with a group of healthy athletes with physiological LVH to ascertain the reliability of current discriminating structural and functional left ventricular (LV) parameters used to differentiate between the 2 entities.

Methods

Setting

This study was collaboration between 2 specialist cardiomyopathy centers in the United Kingdom and France. These institutions receive direct referrals from preparticipation cardiovascular evaluation of young professional athletes, including those suspected with HCM. St George’s Hospital (London, United Kingdom) and the French Institute of Health and Medical Research (Rennes, France) are dedicated Sports Cardiology centers and work closely with the charitable organization Cardiac Risk in the Young and the French National Sports Ministry, respectively, both of whom conduct National screening programs for elite athletes. Since 2010, both institutions have received referrals from Qatar Orthopedic and Sports Medicine Hospital (Doha, Qatar), which has a highly active cardiovascular screening program that serves the entire Persian Gulf region. All elite athletes receive a 12-lead ECG and 2-dimensional echocardiography as part of these screening programs.9

Athletes With HCM

Between 2000 and 2014, 106 consecutive, young (aged 14–35 years), asymptomatic athletes were diagnosed with HCM. The preliminary cardiac investigations resulting in the diagnosis were conducted during a period when these athletes were still actively engaged in competitive sports and before any decision regarding disqualification or cessation of exercise. Of the 106 athletes, 78 (76%) were detected during sports participation screening, and the remainder were identified through familial screening. All athletes with HCM competed at regional, national, or international level and 86 (81.1%) had performed at national or international level during their career. Athletes with HCM competed in a range of sports, including soccer (n=41, 38.7%), rugby (n=11, 10.4%), basketball (n=11, 10.4%), tennis (n=7, 6.6%), cycling (n=4, 3.8%), handball (n=4, 3.8%), distance running (n=4, 3.8%), swimming (n=3, 2.8%), and a mix of other sports (n≤2/sport; n=21, 19.8%). All individuals had baseline blood pressures of <140/90 mm Hg.

The diagnosis of HCM was based on LVH >16 mm in any myocardial segment, as assessed on echocardiography and cardiac MRI (CMRI), in the absence of another cardiac disorder or systemic condition capable of producing the same magnitude of LVH.10,11 In cases of mild LVH, HCM was diagnosed in the context of a combination of features, including (1) identification of HCM in a first-degree relative; (2) nonconcentric patterns of LVH; (3) dynamic left ventricular outflow tract obstruction; (4) late gadolinium enhancement (LGE) on CMRI; or (5) an established pathogenic gene mutation.2,12 Importantly, the combination of electrocardiographic anomalies and mild concentric LVH were not considered diagnostic of HCM in the absence of additional features.

Sedentary HCM Patients

To establish potential phenotypic differences between individuals with HCM who engage in competitive sport, and those who are sedentary, electrocardiographic, echocardiographic, and CMRI data from athletes with HCM was compared with 101 consecutive sedentary HCM patients of similar age, sex, and ethnicity selected from a database of 550 patients at St George’s Hospital.

Healthy Athletes With Mild LVH

A second comparison was made between 15 of the 106 athletes with HCM who expressed mild concentric LVH (13–16 mm) and 55 healthy athletes with mild physiological LVH (13–16 mm). The latter were selected from a database of 3210 elite athletes evaluated between 2000 and 2012 with ECG and transthoracic echocardiography, as previously reported.9 These athletes competed in a range of sports, including soccer (n=12, 21.8%), rugby (n=8, 14.5%), rowing (n=6, 10.9%), boxing (n=5, 9.1%), cycling (n=4, 7.3%), swimming (n=3, 5.5%), and a mix of other sports (n≤2/sport; n=17, 31%). All healthy athletes underwent cardiopulmonary exercise testing, 24-hour Holter monitoring, and CMRI as part of additional work-up to exclude HCM. Figure 1 summarizes the 2 comparison arms.

Figure 1.

Figure 1. Comparison arms of the study. HCM indicates hypertrophic cardiomyopathy; and LVH, left ventricular hypertrophy.

Investigations in Athletes and Sedentary HCM Patients

All individuals with HCM (both athletes and sedentary patients) and healthy athletes with physiological LVH were evaluated as follows. For the purposes of this study, electrocardiographic and echocardiographic analysis was performed on the presenting ECG and echocardiogram.

Electrocardiography

Electrocardiography was performed using standard 12-lead positions using a GE Marquette Hellige (Milwaukee, USA) or Philips Pagewriter Trim III (Bothel, Washington) as described elsewhere.9 Electrocardiograms were analyzed and deemed normal or abnormal in accordance with current European recommendations.13 T-wave inversion of ≥−0.1 mV in ≥2 leads was considered significant (excluding AVR, V1+lead III in isolation). Biphasic T-wave inversion was counted as abnormal if the negative deflection of the T-wave exceeded ≥−0.1mV. Deep T-wave inversion was defined as a T-wave deflection ≥−0.2mV.

Echocardiography

Two-dimensional echocardiography was performed using either a GE Vivid I (Tirat, Israel), Philips Sonos 7500, Philips iE33, or Philips CPX50 (Bothel, Washington). Standard views were obtained and cavity and wall thickness measurements performed using established guidelines.14 LV wall thickness was measured in the parasternal long axis at end-diastole and the parasternal short axis at end-diastole at the levels of the mitral valve, papillary muscles, and apex, with the maximal LV wall thickness defined as the greatest measurement obtained. The relative wall thickness was derived by dividing the sum of the end diastolic LV septal and posterior wall thicknesses by the left ventricular end diastolic dimension (LVEDD). Pulsed Doppler recordings were performed at the distal margins of the mitral valve leaflets for early (E) and late (A) diastolic velocities. Tissue Doppler imaging of septal and lateral mitral annular movement was recorded from the apical 4-chamber views to obtain systolic (S′) and diastolic early (E′) and late (A′) peak velocities.15 The ratio of the E velocity to the E′ septal and lateral annular velocities were averaged to provide an index of diastolic function.16 Left ventricular ejection fraction was calculated from LV volumes using Simpson’s rule.14

Further Investigations

Further investigations in all individuals with HCM included a maximal exercise tolerance test, 24-hour Holter monitor, and CMRI.17 Additionally, athletes with HCM were subject to an upright cardiopulmonary exercise test using a COSMED E100w cycle ergometer (Rome, Italy).18

Ethical and Institutional Review Board Approval

Ethical approval was granted by the National Research Ethics Service, Essex 2 Research Ethics Committee in the United Kingdom, the French Ministry of health and youth in France, and Shafallah Medical Genetic Center in Qatar. The study was approved by an institutional review committee, and all participants gave informed consent.

Statistical Analysis

Data were expressed as mean±standard deviation or percentages as appropriate and analyzed using IBM SPSS software, version 20 (Armonk, NY). Continuous variables were tested for normality using the Kolmogorov–Smirnov test. Group differences were tested using Student’s t test or Mann–Whitney U test for normally and non-normally distributed variables, respectively. The chi-squared test or Fisher exact test was used as appropriate to test group differences of proportions. To identify the most parsimonious predictors of athletic status in HCM patients, stepwise logistic regression (forward likelihood ratio) was used. Variables included in the model consisted of those identified as significant predictors of athletic status in univariate analysis and those considered clinically important. Receiver operating characteristic curve analysis was used to test the sensitivity and specificity of those variables that showed significant differences between athletes with morphologically mild concentric HCM and healthy athletes with physiological LVH. Optimal cut-off values, defined as the best compromise between sensitivity and specificity, were calculated by Youden’s Index. Significance was defined as a 2-tailed P value of <0.05 throughout.

Results

Comparison of Athletes With HCM to Sedentary HCM Patients

Demographics

There were no significant differences between athletes with HCM and sedentary HCM patients with respect to age, sex, ethnicity, body surface area, and blood pressure profile (Table 1). A higher proportion of sedentary patients had a family history of HCM, a family history of sudden cardiac death, or a cardiac murmur.

Table 1. Demographics of Athletes With HCM and Sedentary HCM Patients

ParameterAthletes With HCM, n=106Sedentary HCM Patients, n=101P Value
Age at presentation, y24.3±6.925.8±6.00.101
Male sex, %94.390.10.253
Ethnicity, %0.763
 White59.464.4
 Black33.328.7
 Asian7.56.9
Body surface area, m21.95±0.182.00±0.270.299
Systolic blood pressure, mm Hg122.7±11.9121.27±14.80.443
Diastolic blood pressure, mm Hg72.7±10.774.1±10.70.537
Family history of HCM or SCD, %26.447.50.002
Murmur on examination, %16.533.70.005

HCM indicates hypertrophic cardiomyopathy; and SCD, sudden cardiac death.

Electrocardiographic Changes

The electrocardiographic differences between athletes with HCM and sedentary HCM patients are illustrated in Table 2. T-wave inversion was common in all individuals with HCM, but was more frequent in the athletic cohort compared with sedentary patients (96.2% versus 84.2%, P=0.003). The majority of T-wave inversion in both groups was deep and affected the lateral leads. There were no significant differences between the groups with respect to other abnormal ECG patterns.13 Two athletes with HCM had an entirely normal ECG. The diagnosis of HCM in these individuals was triggered by an abnormal echocardiogram and a positive family history for the condition.

Table 2. Electrocardiographic Characteristics of Athletes With HCM and Sedentary HCM Patients

Electrocardiographic ParameterAthletes With HCM, n=106Sedentary HCM Patients, n=101P Value
Heart rate, bpm59.9±9.967.1±14.3<0.001
Sinus rhythm, %10098.00.145
1st degree heart block, %11.58.60.496
Left-axis deviation, %7.511.90.291
Right-axis deviation, %1.95.90.130
Left bundle branch block, %0.05.00.020
Right bundle branch block, %1.94.00.374
Right ventricular hypertrophy*, %11.518.90.145
Left ventricular hypertrophy*, %61.351.50.154
Left atrial enlargement, %39.637.60.768
Right atrial enlargement, %17.917.80.985
Pathological Q-waves, %23.619.80.510
TWI, %96.284.20.003
 Confined to V1–V40.94.00.158
 Extending to inferior leads9.46.90.512
 Extending to lateral leads85.873.30.024
Deep TWI, %85.773.30.027
ST-segment elevation, %63.849.50.038
ST-segment depression, %57.142.60.049
QRS fragmentation, %22.339.60.008

HCM indicates hypertrophic cardiomyopathy; and TWI, T-wave inversion.

*By Sokolow–Lyon criteria.

Structural Changes

The echocardiographic and CMRI characteristics of athletes with HCM and sedentary HCM patients are presented in Table 3. Athletes with HCM exhibited a lower mean maximal left ventricular wall thickness compared with sedentary patients (15.8±3.4 versus 19.7±6.5 mm, P<0.001) and a larger LVEDD (47.8±6.0 versus 44.3±7.7 mm, P<0.001). Correspondingly, the relative wall thickness was smaller in athletes with HCM compared with sedentary patients (0.57±0.21 versus 0.71±0.34, P<0.001). In total, 15 (14.2%) athletes with HCM revealed an LVEDD of >54 mm. Important differences were observed in the pattern of LVH between athletes with HCM and sedentary patients. Asymmetrical septal hypertrophy was the predominant pattern in both groups, but athletes with HCM were more likely to exhibit apical LVH (35.8% versus 11.9%, P<0.001; Figure 2). Of note, only 15 (14.2%) athletes with HCM exhibited concentric LVH.

Table 3. Structural Characteristics of Athletes With HCM and Sedentary HCM Patients on Echocardiography and Cardiac MRI

Structural CharacteristicAthletes With HCM, n=106Sedentary HCM Patients, n=101P Value
Echocardiography
 Left atrial dimension, mm38.1±6.538.7±8.60.347
 Left ventricular end diastolic dimension, mm47.8±6.044.3±7.7<0.001
 Maximal left ventricular wall thickness, mm15.8±3.419.7±6.5<0.001
 Relative wall thickness0.57±0.210.71±0.34<0.001
 Fractional shortening, %41.1±9.340.5±10.00.391
 LVEF, %67.7±6.658.6±12.2<0.001
 Systolic anterior motion of the mitral valve leaflets at rest, %8.123.80.002
 Resting left ventricular outflow tract gradient ≥30 mm Hg, %2.012.00.006
 Mitral inflow E-wave, m/s0.79±0.190.75±0.170.173
 Mitral inflow A-wave, m/s0.49±0.170.52±0.160.061
 Mitral E/A ratio1.73±0.531.55±0.510.018
 Mitral valve deceleration time193.9±49.0193.6±55.70.974
 Lateral S′, m/s0.10±0.020.08±0.02<0.001
 Lateral E′, m/s0.13±0.040.10±0.04<0.001
 Lateral E/E6.7±2.48.9±3.9<0.001
 Septal E′, m/s0.09±0.030.07±0.02<0.001
 Septal E/E9.3±3.212.6±5.3<0.001
 Average E/E7.9±2.410.7±3.9<0.001
 Mitral regurgitation >mild, %2.930.7<0.001
 Ventricular hypertrophy pattern, %<0.001
  Septal45.350.5
  Apical35.811.9
  Concentric14.22.0
  Mixed4.735.6
Cardiac MRI, %66.066.3
  Left ventricular end diastolic volume index, mL/m283.6±16.873.4±19.50.021
  LVEF, %70.8±7.972.5±8.90.221
 Left ventricular mass index, g/m2102.6±31.1104.4±42.30.931
 Late gadolinium enhancement, %33.040.60.258

HCM indicates hypertrophic cardiomyopathy; and LVEF, left ventricular ejection fraction.

Figure 2.

Figure 2. Differences in LVH patterns between athletes with HCM and sedentary HCM patients. HCM indicates hypertrophic cardiomyopathy; and LVH, left ventricular hypertrophy.

The LV end-diastolic volumes measured on CMRI were greater in athletes with HCM compared with sedentary HCM patients. There were, however, no differences in LV mass between the 2 groups. A similar proportion of athletes with HCM and sedentary patients revealed LGE.

Functional Changes

Athletes with HCM showed superior LV diastolic indices compared with sedentary HCM patients, as assessed by Tissue Doppler imaging in both the septal and lateral mitral annulus (Table 3). The average E/E′ ratio was smaller in athletes with HCM compared with sedentary HCM patients (7.9±2.4 versus 10.7±3.9, P<0.001). The majority of athletes with HCM exhibited diastolic indices within traditionally accepted normal limits;19,20 92.5% had an average E/E′ <12,21 59.4% had a septal E′ ≥0.09 m/s, and 86.8% had a lateral E′ ≥0.09 m/s.

Athletes with HCM demonstrated a lower prevalence of systolic anterior motion of the mitral valve leaflets (SAM), left ventricular outflow tract pressure gradients of ≥30 mm Hg under basal conditions, and moderate or severe mitral regurgitation compared with sedentary patients.

Exercise Testing and Holter Monitoring

Athletes with HCM obtained mean peak oxygen consumption (pVO2) of 110%±24% of that predicted for age and sex and a quarter (25.5%) achieved a pVO2 of ≥120% of predicted. Fourteen (13.2%) athletes with HCM displayed abnormalities on exercise testing. Nine athletes with HCM (8.5%) demonstrated a blunted blood pressure response to exercise (systolic rise of <25 mm Hg) compared with 23 sedentary HCM patients (22.8%, P=0.004). Exercise-induced arrhythmias were observed in 6 (5.6%) athletes with HCM, specifically nonsustained ventricular tachycardia (n=1); supraventricular tachycardia (n=2); atrial fibrillation (n=1); and frequent ventricular ectopics (n=2).

During ambulatory 24-hour Holter monitoring, 13 athletes with HCM (12.3%) revealed arrhythmias, specifically nonsustained ventricular tachycardia (n=9); supraventricular tachycardia (n=2); and atrial fibrillation (n=2). A further 10 athletes with HCM (9.4%) demonstrated nonspecific findings, namely couplets and triplets (n=7), frequent (>2000/per 24 hours) ventricular ectopic beats (n=2), and a junctional rhythm (n=1).

Multivariable Analysis

Stepwise logistic regression revealed the following variables to be the strongest predictors of athletic status (Table 4): (1) apical or concentric patterns of LVH as opposed to a mixed patterns; (2) lower maximum LV wall thickness; (3) absence of >mild mitral regurgitation; (4) ST-segment elevation on the ECG; (5) absence of QRS fragmentation on the ECG. The final model had a Nagelkerke R2 of 0.524.

Table 4. Univariable and Multivariable Predictors of Athletic Status in Patients With HCM

UnivariateP ValueMultivariateP Value
Age, per year0.97 (0.93–1.01)0.103
Sex (female/male)0.55 (0.19–1.56)0.259
Family history of hypertrophic cardiomyopathy/sudden cardiac death0.40 (0.22–0.71)0.002
Murmur on examination0.39 (0.20–0.77)0.006
Heart rate, per 10 bpm0.61 (0.47–0.79)<0.001
T-wave inversion4.8 (1.55–14.9)0.007
ST elevation1.80 (1.03–3.14)0.0393.11 (1.19–8.11)0.020 (4)
 ST depression1.73 (1.0–3.0)0.052
QRS fragmentation0.44 (0.24–0.81)0.0090.31 (0.10–0.91)0.033 (5)
 LV end diastolic diameter, mm1.08 (1.03–1.12)0.001
Maximum LV wall thickness, mm0.88 (0.83–0.94)<0.0010.86 (0.75–0.98)0.023 (2)
 Systolic anterior motion of anterior mitral valve leaflets (at rest)0.28 (0.12–0.66)0.004
 LV outflow tract gradient >30 mm Hg (at rest)0.15 (0.03–0.69)0.015
 Mitral E/A1.97 (1.11–3.49)0.020
 Average E/E0.74 (0.66–0.83)<0.001
Mitral regurgitation (>mild)0.07 (0.02–0.23)<0.0010.16 (0.04–0.72)0.017 (3)
LV hypertrophy pattern<0.001<0.001 (1)
 Apical versus mixed22.8 (7.3–71.18)<0.00121.81 (4.77–99.81)<0.001
 Septal versus mixed6.78 (2.46–18.7)<0.0019.15 (2.17–38.63)0.003
 Concentric versus mixed54 (9.4–309.8)<0.00144.79 (4.55–441.37)0.001
Nonsustained ventricular tachycardia on 24 h Holter0.32 (0.13–0.75)0.009
Documented atrial fibrillation0.09 (0.02–0.38)0.001

In the multivariable P value column, the numbers in parentheses indicate the order of significance of the independent variables selected in the final forward likelihood ratio model. HCM indicates hypertrophic cardiomyopathy; and LV, left ventricular.

Comparison of Athletes With Morphologically Mild HCM to Healthy Athletes With Physiological LVH

The majority of athletes with HCM exhibited either a left ventricular wall thickness >16 mm (n=48; 45.3%) and nonconcentric patterns of LVH (n=91; 85.8%), which would be considered diagnostic of HCM based on current algorithms.25

Fifty-eight athletes with HCM revealed morphologically mild LVH (13–16 mm). Of these, only a small minority exhibited concentric LVH (n=15; 14.2%) consistent with the conventional gray zone.25 These athletes had a higher prevalence of T-wave inversion compared with athletes with physiological LVH (100% versus 5.5%, P<0.001). Deep T-wave inversion in the lateral leads (93.3%), pathological Q-waves (26.7%), and ST-segment depression (46.7%) were observed exclusively in athletes with HCM.

Athletes with mild concentric HCM revealed smaller LV cavities (49.3±4.4 mm versus 54.9±4.7 mm, P<0.001) and a higher E/E′ ratio (7.1±2.0 versus 5.5±1.1, P≤0.001) compared with athletes with physiological LVH. A small proportion (13.3%) of athletes with mild concentric HCM revealed an LVEDD of >54 mm, 66.7% had a septal E′ of ≥0.09 m/s and 93.3% had a lateral E′ ≥0.09 m/s. All 15 athletes showed an average E/E′ of <12 and 87% had a normal left atrial dimension. Receiver operating characteristic curve analysis demonstrated that most structural and functional parameters had poor ability to differentiate between morphologically mild concentric HCM and physiological LVH in athletes (Table 5). Only an LVEDD ≤51 mm and septal E′ ≤0.11 m/s showed good discriminating ability (area under the curve >0.8).

Table 5. Receiver Operating Characteristic Analysis Evaluating Conventional Structural and Functional Echocardiographic Parameters for Distinguishing Physiological LVH in Healthy Athletes (n=55) From Pathological LVH in Athletes With Mild Concentric HCM (n=15)

VariableArea Under the CurveSensitivity, %Specificity, %P Value
LVEDD ≤51 mm*0.81972.781.8<0.001
LVEDD ≤54 mm0.81981.861.8
Average E/E′ >6.6*0.65360.079.00.171
Average E/E′ >120.6530.0100
Relative wall thickness >0.45*0.76081.865.40.013
Lateral E′ ≤0.15 m/s*0.70090.047.40.043
Lateral E′ ≤0.09 m/s0.70020.0100
Left atrium ≤38 mm*0.60272.745.50.263
Left atrium ≤40 mm0.60290.923.6
Septal E′ ≤0.11 m/s*0.87788.968.4<0.001
Septal E′ ≤0.09 m/s0.87755.6100
Mitral A wave >0.40*0.77110050.0<0.001
Mitral A wave >0.460.77172.767.3

HCM indicates hypertrophic cardiomyopathy; LVEDD, left ventricular end diastolic dimension; and LVH, left ventricular hypertrophy.

*Value calculated by Youden’s Index as best compromise between sensitivity and specificity.

Sensitivity and specificity at traditional cut-off values.

Role of Other Investigations

None of the 15 athletes with mild concentric HCM revealed abnormalities on exercise testing. One athlete (6.7%) with mild concentric HCM demonstrated arrhythmias on 24-hour Holter monitoring, namely nonsustained ventricular tachycardia. None of the healthy athletes with physiological LVH demonstrated abnormalities on exercise testing or Holter monitoring.

Athletes with mild concentric HCM obtained a similar percentage predicted pVO2 compared with athletes with physiological LVH (113%±22% versus 122%±14%, P=0.057). Five (33.3%) athletes with mild concentric HCM obtained a pVO2 of >120% of that predicted compared with 31 (56.9%) athletes with physiological LVH. Four athletes with mild concentric HCM (26.7%) revealed LGE on CMRI compared with none of the athletes with physiological LVH.

Discussion

Hypertrophic cardiomyopathy is generally characterized by reduced functional capacity,18,22 and most patients are unable to engage in competitive sport involving high-intensity exercise.23 However, several reports in the literature have described affected individuals capable of extraordinary feats of athletic achievement.68 Our knowledge of the ability of these individuals to perform at such a high level, and whether their phenotype differs from ordinary (sedentary) patients, is limited. Furthermore, the superadded effect of cardiac loading conditions associated with exercise itself on the HCM phenotype is also unknown. The differentiation of physiological LVH from morphologically mild HCM is challenging, and an erroneous diagnosis has potentially serious consequences. When faced with such a dilemma, the differentiation places considerable reliance on other structural and functional LV parameters, assuming that they are similar to those in sedentary HCM patients. The present study provided a unique opportunity for examining the HCM phenotype in affected young asymptomatic athletes.

Differences in Athletes With HCM and Sedentary HCM Patients

Compared with sedentary HCM patients, athletes with HCM revealed milder LVH and the apical variant of the condition in more than a third of the cohort, both of which were independent predictors of athletic status (Figure 3). The apical variant of HCM could also be classified into the mild LVH category because the hypertrophy is localized to a small segment of the left ventricle and may not affect the dynamics of the chamber as much as more generalized hypertrophy.

Figure 3.

Figure 3. The clinical profile of athletes with hypertrophic cardiomyopathy (HCM). This illustration summarizes the electrocardiographic, structural, and functional characteristics that differ between athletes with HCM and sedentary HCM patients. A combination of these features may explain why athletes with HCM are able to compete in sporting activities at an extraordinarily high level, in contrast to most patients with HCM who show functional limitation. Only a minority of athletes with HCM fall within the true gray zone between physiological and pathological left ventricular hypertrophy (LVH); these individuals may exhibit left ventricular (LV) cavity dilatation and normal indices of diastolic function, which cannot therefore be used to exclude the diagnosis of HCM in an athlete in isolation. LVWT indicates left ventricular wall thickness.

Similar to studies comparing healthy athletes with sedentary controls, athletes with HCM showed larger LV cavity dimensions compared with sedentary HCM patients. Indeed, only a small proportion of sedentary HCM patients (3%) showed dimensions exceeding 54 mm compared with 14.2% of the athletes with HCM. It is generally recognized that a dilated left ventricle is usually observed in the end stages of HCM in ≈5% of patients and is associated with poor contraction and functional capacity.24 In the case of athletes with HCM, the enlarged LV cavity is likely to represent physiological adaptation to increased cardiac workload associated with exercise. The preservation of radial contraction, longitudinal systolic function, and high pVO2 favors a physiological process.

Most athletes with HCM showed normal indices of diastolic function according to conventional cut-off values on Tissue Doppler imaging. Only 2% of athletes with HCM revealed left ventricular outflow tract obstruction at rest. Thus, the combination of a larger LV volume, normal LV diastolic function, and absence of dynamic left ventricular outflow tract obstruction likely facilitate the augmentation of stroke volume, which is the major determinant of peak exercise capacity in HCM in the presence of adequate LV filling.25,26

Myocardial fibrosis is a commonly cited explanation for a noncompliant left ventricle and impaired myocardial relaxation.27 However, a similar proportion of athletes with HCM and sedentary patients demonstrated LGE on CMRI. These results underscore the importance of CMRI as a diagnostic tool in athletes with a high index of suspicion for HCM. At the same time, however, our results suggest that superior methods of detecting generalized fibrosis are necessary to study the pathophysiology of HCM.28 It is also possible that athletes with HCM had a lower ischemic burden because of the absence of severe LVH and mechanical LV obstruction, which enabled more exercise, despite a similar magnitude of scarring.

Differentiation of Athlete’s Heart From Morphologically Mild HCM

Previous studies have reported several parameters, which are now regarded as good discriminators between athlete’s heart and morphologically mild HCM, including LV cavity dimension, indices of LV diastolic function, and left atrial dimesnison.2,3,11,29 A recent report suggested an LV cavity dimension of >54 mm to be a particularly good discriminator, favoring physiological LVH over HCM with both a sensitivity and specificity of 100%.4 However, these studies are limited by the fact that they relied on data from sedentary HCM patients, who do not provide an appropriate comparison group.

Our observations suggest that the vast majority of athletes with HCM exhibit a maximal left ventricular wall thickness of ≥16 mm and nonconcentric patterns of LVH, which would be diagnostic of HCM based on current algorithms for differentiating physiological LVH from morphologically mild HCM. Indeed, only 14% of athletes with HCM seem to fall into the conventional and often challenging gray zone of mild (13–16 mm), concentric LVH. Among athletes in this gray zone, our analysis revealed that an LV cavity ≤51 mm favoring a diagnosis of HCM offers the best compromise between sensitivity and specificity when discriminating physiological from pathological LVH. A value of ≤54 mm had better sensitivity, but at the expense of higher false-positive results (Table 5). In contrast with a recent report,4 our study failed to identify any cut off value for left atrial diameter that adequately distinguished physiology from pathology. Indices of diastolic function were normal in most athletes with HCM and should not be used in isolation to exclude HCM in an athlete with LVH.

This study reaffirms the value of the ECG in diagnosing HCM in athletes. We concede that our cohort is heavily biased because ECG anomalies, particularly T-wave inversion, were the primary reason for referral after preparticipation screening. The fact remains, however, that 96% of athletes and 84% of patients with HCM exhibited pathological T-wave inversion, the great majority of which involved the lateral leads. Moreover, 57% of athletes with HCM exhibited ST-segment depression and almost a quarter revealed pathological Q-waves. In contrast, none of the athletes with physiological LVH demonstrated deep T-wave inversion in the lateral leads, ST-segment depression, or pathological Q-waves. None of the athletes with HCM exhibited isolated voltage criterion for LVH, reinforcing the message that large QRS complexes in isolation are not necessarily indicative of quiescent HCM.9

Exercise testing and Holter monitoring would have facilitated the diagnosis in only 19% of athletes with HCM. Contrary to a previous publication,18 25% of athletes with HCM achieved a pVO2 >120% of predicted. In line with a recent publication,30 the value of CMRI is underscored by the detection of LGE in a third of athletes with HCM, in addition to its ability to delineate the pattern of LVH.

Clinical Implications

Our results have significant practical implications for differentiating physiological LVH from morphologically mild HCM. Most athletes with HCM exhibit features which would facilitate the diagnosis of HCM if current diagnostic algorithms are applied. Among the small proportion of athletes with mild concentric LVH of 13 to 16 mm, an increased LV cavity size, normal diastolic function, or superior indices of functional capacity should not be used in isolation to exclude HCM. An exercise test can help facilitate the diagnosis in a fifth of cases, and CMRI is diagnostic in one third of cases after ECG and echocardiography. In athletes with a high index of suspicion for HCM because of the presence of LVH and coexisting repolarization anomalies, the assessing physician should use the whole complement of noninvasive cardiac tests to assist the diagnosis. Although not assessed specifically in this study, detraining,8,31 familial evaluation, and genetic testing, though challenging, may also have important additional roles.

Limitations

The authors recognize that a small proportion of athletes with HCM may not have been identified during the screening process given the heterogeneity and aged-related penetrance of the condition, resulting in ascertainment bias. However, the use of history, ECG, and echocardiography to screen all athletes coupled with repeat interval screening at later dates should have limited this number to a minimum. In view of the small number of athletes with mild concentric LVH, it was not feasible to confidently identify independent discriminators of pathological versus physiological LVH using logistic regression. The authors recognize the limitations of receiver operating characteristic curve analysis in isolation and acknowledge the need for large, purposefully built cohorts that aim to identify independent predictors of HCM in athletes with mild concentric LVH.

Conclusions

Athletes with HCM exhibit qualitatively similar physiological cardiac adaptation to normal healthy athletes. An important minority of athletes with HCM (14%) constitute the conventional gray zone of mild (13–16 mm) concentric LVH. In such cases, a large LV cavity or normal indices of diastolic function alone are insufficient to differentiate pathological from physiological LVH. Conventional echocardiographic parameters should be complemented by ECG, exercise stress testing, and CMRI to minimize the risk of false reassurance.

Acknowledgments

We thank Cardiac Risk in the Young for providing portable echocardiography equipment and ECG machines used in the United Kingdom.

Footnotes

Correspondence to Sanjay Sharma, MD, St George’s University of London, Cardiovascular Sciences Cranmer Terrace, London, SW17 0RE, United Kingdom. E-mail

References

  • 1. Maron BJ, Doerer JJ, Haas TS, Tierney DM, Mueller FO.Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980-2006.Circulation. 2009; 119:1085–1092. doi: 10.1161/CIRCULATIONAHA.108.804617.LinkGoogle Scholar
  • 2. 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; 91:1596–1601.LinkGoogle Scholar
  • 3. Maron BJ.Distinguishing hypertrophic cardiomyopathy from athlete’s heart: a clinical problem of increasing magnitude and significance.Heart. 2005; 91:1380–1382. doi: 10.1136/hrt.2005.060962.CrossrefMedlineGoogle Scholar
  • 4. Caselli S, Maron MS, Urbano-Moral JA, Pandian NG, Maron BJ, Pelliccia A.Differentiating left ventricular hypertrophy in athletes from that in patients with hypertrophic cardiomyopathy.Am J Cardiol. 2014; 114:1383–1389. doi: 10.1016/j.amjcard.2014.07.070.CrossrefMedlineGoogle Scholar
  • 5. Basavarajaiah S, Boraita A, Whyte G, Wilson M, Carby L, Shah A, Sharma S.Ethnic differences in left ventricular remodeling in highly-trained athletes relevance to differentiating physiologic left ventricular hypertrophy from hypertrophic cardiomyopathy.J Am Coll Cardiol. 2008; 51:2256–2262. doi: 10.1016/j.jacc.2007.12.061.CrossrefMedlineGoogle Scholar
  • 6. Maron BJ, Klues HG.Surviving competitive athletics with hypertrophic cardiomyopathy.Am J Cardiol. 1994; 73:1098–1104.CrossrefMedlineGoogle Scholar
  • 7. Wilson MG, Chandra N, Papadakis M, O’Hanlon R, Prasad SK, Sharma S.Hypertrophic cardiomyopathy and ultra-endurance running - two incompatible entities?J Cardiovasc Magn Reson. 2011; 13:77. doi: 10.1186/1532-429X-13-77.CrossrefMedlineGoogle Scholar
  • 8. Basavarajaiah S, Wilson M, Whyte G, Shah A, McKenna W, Sharma S.Prevalence of hypertrophic cardiomyopathy in highly trained athletes: relevance to pre-participation screening.J Am Coll Cardiol. 2008; 51:1033–1039. doi: 10.1016/j.jacc.2007.10.055.CrossrefMedlineGoogle Scholar
  • 9. Sheikh N, Papadakis M, Ghani S, Zaidi A, Gati S, Adami PE, Carré F, Schnell F, Wilson M, Avila P, McKenna W, Sharma S.Comparison of electrocardiographic criteria for the detection of cardiac abnormalities in elite black and white athletes.Circulation. 2014; 129:1637–1649. doi: 10.1161/CIRCULATIONAHA.113.006179.LinkGoogle Scholar
  • 10. Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H, Seidman CE, Towbin JA, Udelson JE, Yancy CW; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.J Am Coll Cardiol. 2011; 58:e212–e260. doi: 10.1016/j.jacc.2011.06.011.CrossrefMedlineGoogle Scholar
  • 11. 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. doi: 10.1056/NEJM199101313240504.CrossrefMedlineGoogle Scholar
  • 12. Maron BJ, Pelliccia A.The heart of trained athletes: cardiac remodeling and the risks of sports, including sudden death.Circulation. 2006; 114:1633–1644. doi: 10.1161/CIRCULATIONAHA.106.613562.LinkGoogle Scholar
  • 13. Corrado D, Pelliccia A, Heidbuchel H, Sharma S, Link M, Basso C, Biffi A, Buja G, Delise P, Gussac I, Anastasakis A, Borjesson M, Bjørnstad HH, Carrè F, Deligiannis A, Dugmore D, Fagard R, Hoogsteen J, Mellwig KP, Panhuyzen-Goedkoop N, Solberg E, Vanhees L, Drezner J, Estes NA, Iliceto S, Maron BJ, Peidro R, Schwartz PJ, Stein R, Thiene G, Zeppilli P, McKenna WJ; Section of Sports Cardiology, European Association of Cardiovascular Prevention and Rehabilitation. Recommendations for interpretation of 12-lead electrocardiogram in the athlete.Eur Heart J. 2010; 31:243–259. doi: 10.1093/eurheartj/ehp473.CrossrefMedlineGoogle Scholar
  • 14. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ; Chamber Quantification Writing Group; American Society of Echocardiography’s Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.J Am Soc Echocardiogr. 2005; 18:1440–1463. doi: 10.1016/j.echo.2005.10.005.CrossrefMedlineGoogle Scholar
  • 15. Quiñones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA; Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography.J Am Soc Echocardiogr. 2002; 15:167–184.CrossrefMedlineGoogle Scholar
  • 16. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelista A.Recommendations for the evaluation of left ventricular diastolic function by echocardiography.J Am Soc Echocardiogr. 2009; 22:107–133. doi: 10.1016/j.echo.2008.11.023.CrossrefMedlineGoogle Scholar
  • 17. Papadakis M, Carre F, Kervio G, Rawlins J, Panoulas VF, Chandra N, Basavarajaiah S, Carby L, Fonseca T, Sharma S.The prevalence, distribution, and clinical outcomes of electrocardiographic repolarization patterns in male athletes of African/Afro-Caribbean origin.Eur Heart J. 2011; 32:2304–2313. doi: 10.1093/eurheartj/ehr140.CrossrefMedlineGoogle Scholar
  • 18. Sharma S, Elliott PM, Whyte G, Mahon N, Virdee MS, Mist B, McKenna WJ.Utility of metabolic exercise testing in distinguishing hypertrophic cardiomyopathy from physiologic left ventricular hypertrophy in athletes.J Am Coll Cardiol. 2000; 36:864–870.CrossrefMedlineGoogle Scholar
  • 19. Nagueh SF, McFalls J, Meyer D, Hill R, Zoghbi WA, Tam JW, Quiñones MA, Roberts R, Marian AJ.Tissue Doppler imaging predicts the development of hypertrophic cardiomyopathy in subjects with subclinical disease.Circulation. 2003; 108:395–398. doi: 10.1161/01.CIR.0000084500.72232.8D.LinkGoogle Scholar
  • 20. Vinereanu D, Florescu N, Sculthorpe N, Tweddel AC, Stephens MR, Fraser AG.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.CrossrefMedlineGoogle Scholar
  • 21. Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A, Limongelli G, Mahrholdt H, McKenna WJ, Mogensen J, Nihoyannopoulos P, Nistri S, Pieper PG, Pieske B, Rapezzi C, Rutten FH, Tillmanns C, Watkins H, O’Mahony C, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Alfonso F, Basso C, Cardim NM, Gimeno JR, Heymans S, Holm PJ, Keren A, Lionis C, Muneretto C, Priori S, Salvador MJ, Wolpert C.2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).Eur Heart J. 2014;1–55.MedlineGoogle Scholar
  • 22. Sharma S, Elliott P, Mahon N, Whipp B, Whyte G, Jones S, Mckenna WJ.Utility of cardiopulmonary exercise in the assessment of clinical determinants hypertrophic cardiomyopathy.Am J Cardiol. 2000; 86:162–168.CrossrefMedlineGoogle Scholar
  • 23. Maron BJ, Bonow RO, Cannon RO, Leon MB, Epstein SE.Hypertrophic cardiomyopathy. Interrelations of clinical manifestations, pathophysiology, and therapy (1).N Engl J Med. 1987; 316:780–789. doi: 10.1056/NEJM198703263161305.CrossrefMedlineGoogle Scholar
  • 24. Harris KM, Spirito P, Maron MS, Zenovich AG, Formisano F, Lesser JR, Mackey-Bojack S, Manning WJ, Udelson JE, Maron BJ.Prevalence, clinical profile, and significance of left ventricular remodeling in the end-stage phase of hypertrophic cardiomyopathy.Circulation. 2006; 114:216–225. doi: 10.1161/CIRCULATIONAHA.105.583500.LinkGoogle Scholar
  • 25. Chikamori T, Counihan PJ, Doi YL, Takata J, Stewart JT, Frenneaux MP, McKenna WJ.Mechanisms of exercise limitation in hypertrophic cardiomyopathy.J Am Coll Cardiol. 1992; 19:507–512.CrossrefMedlineGoogle Scholar
  • 26. Lele SS, Thomson HL, Seo H, Belenkie I, McKenna WJ, Frenneaux MP.Exercise capacity in hypertrophic cardiomyopathy. Role of stroke volume limitation, heart rate, and diastolic filling characteristics.Circulation. 1995; 92:2886–2894.LinkGoogle Scholar
  • 27. Moreo A, Ambrosio G, De Chiara B, Pu M, Tran T, Mauri F, Raman SV.Influence of myocardial fibrosis on left ventricular diastolic function: noninvasive assessment by cardiac magnetic resonance and echo.Circ Cardiovasc Imaging. 2009; 2:437–443. doi: 10.1161/CIRCIMAGING.108.838367.LinkGoogle Scholar
  • 28. Puntmann VO, Voigt T, Chen Z, Mayr M, Karim R, Rhode K, Pastor A, Carr-White G, Razavi R, Schaeffter T, Nagel E.Native T1 mapping in differentiation of normal myocardium from diffuse disease in hypertrophic and dilated cardiomyopathy.JACC Cardiovasc Imaging. 2013; 6:475–484. doi: 10.1016/j.jcmg.2012.08.019.CrossrefMedlineGoogle Scholar
  • 29. Lewis JF, Spirito P, Pelliccia A, Maron BJ.Usefulness of Doppler echocardiographic assessment of diastolic filling in distinguishing “athlete’s heart” from hypertrophic cardiomyopathy.Br Heart J. 1992; 68:296–300.CrossrefMedlineGoogle Scholar
  • 30. Schnell F, Riding N, O’Hanlon R, Axel Lentz P, Donal E, Kervio G, Matelot D, Leurent G, Doutreleau S, Chevalier L, Guerard S, Wilson MG, Carré F.Recognition and significance of pathological T-wave inversions in athletes.Circulation. 2015; 131:165–173. doi: 10.1161/CIRCULATIONAHA.114.011038.LinkGoogle Scholar
  • 31. Basavarajaiah S, Wilson M, Junagde S, Jackson G, Whyte G, Sharma S, Roberts WO.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; 40:727–9; discussion 729. doi: 10.1136/bjsm.2005.024596.CrossrefMedlineGoogle Scholar

CLINICAL PERSPECTIVE

Compared with sedentary hypertrophic cardiomyopathy (HCM) patients, athletes with HCM exhibit a higher prevalence of T-wave inversion, milder left ventricular hypertrophy (LVH), larger cavity dimensions, and superior indices of diastolic function. Fourteen percent of athletes with HCM have an left ventricular end diastolic dimension >54 mm and 93% have an E/E′ of <12. Furthermore, over one-third (36%) of athletes with HCM reveal an apical pattern of LVH, and most (86%) have a magnitude and pattern of hypertrophy consistent with a diagnosis of HCM using conventional definitions. Only a small number (14%) fall within the true gray zone of mild (13–16 mm) concentric LVH. In this small but significant subgroup, conventional discriminators between athlete’s heart and HCM, particularly a large left ventricular cavity or normal indices of diastolic function, are in isolation insufficient to differentiate physiological LVH from HCM. Therefore, when faced with an athlete falling within the gray zone of LVH, physicians involved in athlete preparticipation screening programs should complement echocardiography with ECG, exercise stress testing, and cardiac MRI before making a diagnosis.