Recognition and Significance of Pathological T-Wave Inversions in Athletes
Pathological T-wave inversion (PTWI) is rarely observed on the ECG of healthy athletes, whereas it is common in patients with certain cardiac diseases. All ECG interpretation guidelines for use within athletes state that PTWI (except in leads aVR, III and V1 and in V1–V4 when preceded by domed ST segment in asymptomatic Afro-Caribbean athletes only) cannot be considered a physiological adaptation. The aims of the present study were to prospectively determine the prevalence of cardiac pathology in athletes presenting with PTWI, and to examine the efficacy of cardiac magnetic resonance in the work-up battery of further examinations.
Methods and Results—
Athletes presenting with PTWI (n=155) were investigated with clinical examination, ECG, echocardiography, exercise testing, 24h Holter ECG, and cardiac magnetic resonance. Cardiac disease was established in 44.5% of athletes, with hypertrophic cardiomyopathy (81%) the most common pathology. Echocardiography was abnormal in 53.6% of positive cases, and cardiac magnetic resonance identified a further 24 athletes with disease. Five athletes (7.2%) considered normal on initial presentation subsequently expressed pathology during follow-up. Familial history of sudden cardiac death and ST-segment depression associated with PTWI were predictive of cardiac disease.
PTWI should be considered pathological in all cases until proven otherwise, because it was associated with cardiac pathology in 45% of athletes. Despite echocardiography identifying pathology in half of these cases, cardiac magnetic resonance must be considered routine in athletes presenting with PTWI with normal echocardiography. Although exclusion from competitive sport is not warranted in the presence of normal secondary examinations, annual follow-up is essential to ascertain possible disease expression.
Intense physical training may induce electric and myocardial adaptations that are collectively referred to as the athlete’s heart.1,2 Although the majority of these are physiological and distinct from heart disease, some ECG parameters observed in a minority of athletes present diagnostic conundrums, which are suggestive of pathology. A resting 12-lead ECG is recommended by the European Society of Cardiology3 as part of the preparticipation evaluation for athletes before competitive sport. Several ECG interpretation guidelines have been proposed for use within athletes,2,4 with all underlining that marked pathological T-wave inversion (PTWI) is abnormal and is unrelated to physiological adaptation induced through physical activity.1,2,4,5 PTWI has to be differentiated from the physiological T-wave inversion (T-wave inversion in leads aVR, III, and V1 and in V1–V4 when preceeded by domed ST segments in asymptomatic Afro-Caribbean athletes only).6 This pattern has also been reported as a normal variant pattern of repolarization in Afro-Caribbean athletes and is sometimes referred to as Juvenile Pattern.7,8
Editorial see p 128
Clinical Perspective on p 173
PTWIs are observed in several diseases associated with sudden cardiac death (SCD) in athletes–hypertrophic cardiomyopathy (HCM),3,9,10 dilated cardiomyopathy (DCM), left ventricular noncompaction (LVNC),1,2,4,8 arrhythmogenic right ventricular cardiomyopathy (ARVC),3,11 and myocarditis.2,4,12 Accordingly, athletes presenting with these diseases are at risk of SCD and are usually excluded for competitive and intensive sport.2,4,5,13 Thus, the management of an athlete presenting with PTWI is an extremely challenging issue for the sports cardiologist for 2 reasons9,10,14—first because of the high association between PTWI and cardiac disease, and second because the ECG may be the first and only sign of pathology without actual phenotypic manifestations of disease on secondary investigations.
To plan optimal management and treatment strategies for athletes with PTWI, we and others have proposed that alongside personal symptoms, family history, physical examination, and ECG, secondary investigations should also include transthoracic echocardiography (TTE), maximal exercise testing, 24h Holter ECG, and late gadolinium enhanced cardiovascular MRI (CMR).14 Although TTE is routine and easily available, it is limited in its inability to accurately define processes that are occurring at the myocardial tissue level.14 In contrast, CMR imaging allows definition of abnormal processes occurring at the tissue level, including myocardial edema, fatty infiltration, and importantly, myocardial fibrosis.15 CMR also allows for imaging of myocardial regions not clearly seen on echocardiography such as the left ventricular (LV) anterolateral free wall and the LV apex.
Although these series of secondary investigations have been recommended,14 to our knowledge no study has evaluated the efficacy of these examinations in a large cohort of well-trained athletes presenting with PTWI. The aim of this investigation was to (1) prospectively determine the prevalence of cardiac pathology in athletes presenting with PTWI, and (2) examine the efficacy of including CMR in the battery of further examinations.
Between December 2008 and April 2013, 6372 competitive athletes were referred for precompetitive sporting evaluation (4139 white, 1266 Afro-Caribbean, and 321 West-Asian male athletes and 398 white and 248 Afro-Caribbean female athletes) in a multi-center (n=8) prospective observational study. A total of 155 athletes presented with PTWI and were included in this study. The study was approved by the hospital ethics committee and conducted in accordance with the Declaration of Helsinki. All participants gave informed consent.
Sole inclusion criteria was any asymptomatic athlete with marked PTWI (≥ 2 mm) on a resting 12-Lead ECG in ≥2 leads (Figure 1). Athletes presenting with physiological TWI in leads III, aVR, and V1, and in V1 through V4 when TWI was preceeded by convexed/domed ST segment in Afro-Caribbean athletes only were not included (Figure 2).4,6,16
Exclusion criteria consisted of any personal history of a disease known to adversely affect ECG repolarization patterns, personal symptoms that suggested coronary disease, drug use that may alter ECG repolarization patterns, and known electrolyte disturbance. Furthermore, athletes were excluded if presenting with other ECG patterns suggestive of cardiovascular disease.
Family history (history of cardiomyopathy or sudden death in a first-degree relative <55 years of age), personal symptoms (palpitations, syncope or dizziness, chest pain, exercise related abnormal shortness of breath or fatigue, signs of a recent [≤6 weeks] infectious event, training level), and a physical examination were conducted by a sports cardiologist.
A resting 12-lead ECG was recorded in supine position after 5 mins of rest and analyzed using the Seattle Criteria4 by a sports cardiologist.
Resting Transthoracic Echocardiography
The TTE was performed by a sports cardiologist and analyzed according to American Society of Echocardiography recommendations.17 All measurements were averaged from 3 consecutive cardiac cycles.
A standard cardiac volumes, wall dimension, function, and late gadolinium enhancement (LGE) sequence was performed on a dedicated scanner with full myocardial coverage based on Society for Cardiovascular Magnetic Resonance guidelines. LV and right ventricular (RV) volumes, mass, and function were quantified using customized analysis software by a blinded, single experienced investigator. Wall motion was analyzed based on the 16-segment American Heart Association/American College of Cardiology model. Imaging for LGE to identify fibrosis was performed 5 to 10 minutes after 0.1 mmol/kg gadolinium contrast injection in identical short-axis planes to cine images using a breath-hold inversion-recovery (fast low-angle shot) gradient echo sequence.18
Maximal Exercise Test
Athletes performed a maximal exercise test with continuous ECG monitoring, either on ergocycle or on treadmill in accordance with their sport specificity. Exercise was stopped because of exhaustion or ominous cardiovascular signs or symptoms. Specific attention was paid to a correction or worsening of PTWI, ST depression (>1 mm), or cardiac arrhythmia. Blood pressure was measured every 2 minutes using a manual sphygomanometer. Maximal oxygen consumption (VO2 max) was estimated according to maximal exercise power sustained.19
24h ECG Holter
Athletes underwent 24h Holter including a training session for cardiac arrhythmia evaluation. Nonsustained supraventricular and ventricular tachycardias were defined as ≥3 consecutive premature beats lasting <30 seconds.
Longitudinal Cardiovascular Follow-Up
Athletes with cardiomyopathies were excluded from competition, but were provided with individualized treatment and appropriate review. Athletes presenting with normal initial evaluations underwent yearly cardiovascular evaluation that included clinical examination, ECG, TTE, maximal exercise test, and Holter. CMR was repeated in those athletes who subsequently presented new cardiovascular data suggestive of pathology on review or when the initial CMR was doubtful. Athletes who became symptomatic during follow-up were automatically requested to undergo cardiac evaluation.
For each noninvasive investigation, the investigator was blinded to the result of previous investigation. After complete cardiovascular investigation, athletes were identified as having either (1) a normal heart, (2) a heart suspicious but not diagnostic of cardiac disease, or (3) a cardiac disease diagnosed by 2 sport cardiologists having access to the results of all examinations. A diagnosis of cardiac disease was made in accordance with current guidelines.15,20–24
Because of difficultly distinguishing between the athlete’s heart and mild forms of cardiomyopathy, we used established criteria (see Table 1) to define pathology.22 To diagnose HCM, we used the latest European Society of Cardiology (ESC) guidelines to diagnose and manage HCM.24 The criteria include a familial history of HCM in a first-degree relative, unusual patterns of LV hypertrophy (asymmetrical septal hypertrophy, apical hypertrophy), small left ventricular cavity (left ventricular end diastolic diameter <45 mm), systolic anterior motion and left ventricular outflow obstruction, diastolic dysfunction, LGE on CMR, complex ventricular arrhythmias, and an abnormal VO2 max.1,25 Thus, each diagnosis of HCM was validated with the combination of PTWI, abnormal wall thickness (WT) value (see Table 1) and ≥1 of the criteria documented above. In all cases, modifications to conclusions drawn on the athlete’s first cardiac evaluation where made if during follow-up cardiac disease was expressed; except, however, for the effects of requested detraining on cardiac hypertrophy.
|Hypertrophic cardiomyopathy||13 mm≤ WT <15 mm and LVEDD ≤55 mm in men12 mm≤ WT <15 mm and LVEDD ≤50 mm in women and children||WT ≥15 mm + additional abnormal criteria*|
|Dilated cardiomyopathy||LVEDD >60 mm (32 mm.m-2) and LVEF <50%||LVEDD >65 mm (33 mm.m-2) and LVEF <45%|
|Arrhythmogenic RVcardiomyopathy||Unbalanced RV dilation with normal RV wall motion||Unbalanced RV dilation and RV wall motion abnormality|
|Left ventricularnoncompaction||End systolic NC/C >2and LVEF <50%|
|Myocarditis†||Isolated wall motion abnormality|
|Hypertrophic cardiomyopathy||WT ≥13 mm in men or ≥12 in women and children with no appropriate LV dilation||WT ≥15 mm + additional abnormal criteria*|
|Arrhythmogenic RVcardiomyopathy||RV/LV ≥1.2||RV/LV ≥1.2 and RV wall motion abnormality and /or RV fibrosis|
|Left ventricular non compaction||Diastolic NC/C >2,3and LVEF <50%|
|Dilated cardiomyopathy||LVEDV> 97 mL.m-2. and LVEF <50%||LVEDV >120 mL.m-2and LVEF <45%|
|Myocarditis||Non ischemic LGE|
|Exercise test||Ventricular couplets||NSVT or SVT|
|VO2 max <80% theoretical value|
|Holter ECG||Ventricular couplets||NSVT or SVT|
Data Collection and Statistical Analysis
Statistical analysis was performed using SPSS (v.15; Chicago, IL). Most quantitative variables did not follow a normal distribution, thus a Mann–Whitney test was used for comparison of cardiac variables between athletes presenting with/without cardiac disease. Data were expressed as medians with 25th and 75th percentiles or percentage unless otherwise specified. A P value <0.05 was considered statistically significant.
Of 6372 competitive athletes (n=5726 male and n=646 female) referred for precompetitive sporting evaluation, 155 (2.4%) athletes presented with PTWI median age 27.0 years (range, 20–39) and were included in the study. The prevalence of PTWI from 6372 athletes screened was 2%, 4.8% and 1.9% in white, Afro-Caribbean, and West-Asian male athletes, whereas in females, PTWI was 0.5% and 1.6% in white and Afro-Caribbean athletes. From the 155 athletes with PTWI (149 men; 96.1%), 85 were white (54.8%), 64 were Afro-Caribbean (41.3%), and 6 were West-Asian (3.9%). The athletes trained 10.0 hours/week (range, 6.0–12.0) in either mixed sports (soccer, basketball, handball, or rugby, n=94) or endurance sports (running, cycling, or swimming, n=61).
Results From Primary Investigations
Medical History and Physical Examination
Familial history was positive in 9 (5.8%) athletes; 5 cases of SCD (3 of unknown origin, 1 HCM, 1 DCM) and 4 cases of cardiomyopathy (3 HCM, 1 ARVC). No athlete presented a personal history of known cardiomyopathy. Systolic cardiac murmurs was observed in 16 (10.3%) athletes.
Inferior or lateral PTWI were the most commonly observed abnormalities (83.9%; Table 2), followed by precordial lead PTWI (8.4%) and anterior (V1–V4) PTWI (6.5%). PTWI was largely isolated (43.2%), but associated ECG abnormalities such as ST-segment depression (31%), left atrial hypertrophy (29.0%), and abnormal Q waves (11.0%) were commonly observed.
|Parameters||Global Population (n=155)|
|Heart rate, bpm||59.0 [52.0–65.0]|
|First-degree AV block||19 (12.3%)|
|Second-degree Mobitz 1 AV block||1 (0.6%)|
|Left atrial hypertrophy||45 (29.0%)|
|Abnormal Q wave||17 (11.0%)|
|Sokolow index > 35 mm||83 (53.5%)|
|All precordium||13 (8.4%)|
|Lateral leads||23 (14.8%)|
|I–aVL + V5–V6||7 (4.5%)|
|II–III–aVF + V5–V6||100 (64.5%)|
|II–III–aVF+ V1–V3||1 (0.6%)|
|I–aVL +V1–V3||1 (0.6%)|
|ST depression localization|
|ST depression||48 (31.0%)|
|All precordium||2 (1.3%)|
|I– aVL + V5–V6||4 (2.6%)|
|II– III– aVF||9 (5.8%)|
|II– III– aVF + V5–V6||16 (10.3%)|
The TTE was normal in 86 (55.5%) athletes, with 37 (23.9%) athletes demonstrating an abnormal TTE; 31 cases of HCM, 3 ARVC, 2 LVNC, and 1 case of significant segmental systolic dysfunction (Figure 3). TTE was suspicious but not diagnostic of a cardiac disease in a further 32 (20.6%) athletes (30 with possible HCM and 2 with possible ARVC).
The CMR was normal in 69 (44.5%) athletes and abnormal in 61 (39.3%), with 51 cases of HCM, 4 ARVC, 2 LVNC, and 4 myocarditis. CMR was suspicious but not diagnostic of a cardiac disease in a further 25 (16.1%) athletes (23 possible HCM and 2 possible ARVC).
Maximal Exercise Test and 24h ECG Holter
Exercise testing was obtained in 141 (91%) athletes, with 89.3% demonstrating a normal investigation. Partial or complete normalization of PTWI during exercise was observed in 79% of athletes. However in 8 (5.7%) cases exercise testing was abnormal, 5 athletes demonstrated nonsustained supraventricular tachycardia (3 ARVC, 1 LVNC and 1 myocarditis), 1 athlete demonstrated a drop in blood pressure (LVNC), and 2 athletes demonstrated a poor aerobic capacity (2 HCM). Finally, 7 (5%) athletes presented nonspecific ECG abnormalities during exercise; 1 case of junctionnal tachycardia and 6 cases of ventricular couplets (2 HCM, 1 possible HCM, 1 ARVC, 1 myocarditis, and 1 DCM). Twenty-four-hour ECG Holter was recorded in 109 (70.3%) athletes and was normal in 88% of cases. Nine (8.3%) athletes demonstrated episodes of nonsustained supraventricular tachycardia (6 HCM, 1 ARVC, 2 myocarditis).
Longitudinal Follow-Up Results
After primary investigation, 64 athletes with proven cardiac disease were excluded from competitive sport, with 91 athletes identified as having either a normal heart or a heart suspicious but not diagnostic of cardiac disease and were followed up for 12.0 months (range, 8.0–30.0).
Medical History and Physical Examination
During follow-up, 3 (3.3%) athletes developed ominous symptoms; 1 exercise-related aborted cardiac arrest (unknown cause), 1 episode of syncope (unknown cause but with a familial history of sudden death), and 1 symptoms suggestive of heart failure (1 DCM).
ECG, TTE, Exercise Test, and CMR Imaging
CMR was repeated in 27 athletes; 25 for an initial doubtful CMR and 2 who became symptomatic. No athlete demonstrated a progressive worsening of PTWI or presented new ECG abnormalities during follow-up. However, systolic dysfunction was observed to have developed in 1 athlete with presenting with clinical symptoms (1 DCM). No abnormal exercise test results were observed in followed athletes. One athlete developed HCM with LGE evident, whereas 1 athlete presenting initially as suspicious but not diagnostic of cardiac disease demonstrated apical HCM.
Overall Identification of Pathology
In conclusion, an identifiable cardiac disease was demonstrated in 44.5% (n=69) of athletes presenting with PTWI. HCM (n=56; 36.1%) was the most commonly identified pathology, followed by ARVC (n=4; 2.6%), myocarditis (n=4; 2.6%), LVNC (n=2; 1.3%), DCM (n =1; 0.6%), and arrhythmic event (n=2; 1.3%; Table 3). Although a diagnosis was identified on initial presentation in the majority of athletes (n= 64; 92.8%), a further 5 (7.2%) expressed disease during follow up (Figure 3).
|Cardiac disease||Number of Patients|
|Arrhythmogenic right ventricular cardiomyopathy||4|
|Left ventricular noncompaction||2|
|Arrhythmic events without morphological cardiomyopathy||2|
Hypertrophic Cardiomyopathy Diagnosis
A diagnosis of HCM was established in 54 cases (34.8%) during primary investigation. In 44 cases, the WT was ≥15 mm with a LV end diastolic diameter ≤55 mm. The diagnosis of HCM was confirmed because of the association with ≥1 of the following criteria: family history (n=4), unusual pattern of LV hypertrophy (n=29), LV end diastolic diameter <45 mm (n=12), systolic anterior motion (n=8), diastolic dysfunction (n=3), LGE with MRI (n=19), complex ventricular arrhythmia (n=3), and an abnormal VO2 max (n=1). There were 4 cases of patients presenting a WT ≥15 mm but with a LV end diastolic diameter >55 mm. However, a diagnosis of HCM was made because of the presence of LGE (n=3) and typical apical hypertrophy (n=1). Finally, there were 6 cases presenting a maximal wall thickness between 14 and 15 mm; 3 with LGE, 2 with complex ventricular arrhythmias, and 1 with an LV end diastolic diameter <45 mm and a markedly reduced VO2 max, ultimately leading to the conclusion that the hypertrophy observed was pathological. All patients with pathological hypertrophy underwent a 3-month period of athletic detraining, with 40 patients undergoing 6 months. In all cases, no significant wall thickness regression was observed.
Efficacy of TTE Versus CMR
From the 69 athletes diagnosed with pathology, TTE was abnormal in 53.6% (n = 37), with CMR confirming 100% of all TTE abnormalities (Figure 3). CMR identified cardiac pathology in a further 24 athletes (34.8%); 10 presenting with a heart suspicious but not diagnostic of cardiac disease and 14 athletes demonstrating normal hearts on TTE. Thus, CMR was able to establish a diagnosis in 88.4% (n=61) of athletes.
Clinical Value of the Maximal Exercise Testing and 24h ECG Holter
Maximal exercise testing aided in the diagnosis of cardiac pathology in 8 (5.7%) athletes, of which 7 had ≥1 abnormal imaging result and 1 who presented a suspicious imaging result. Twenty-four-hour ECG Holter was abnormal in 9 athletes, but was associated with abnormal imaging in 7 and in 2 athletes with imaging suspicious but not diagnostic of cardiac disease (Figure 3).
Predictive Factors of Cardiac Disease in Athletes With PTWI
A familial history of SCD or cardiomyopathy in a first-degree relative and ST-segment depression alongside PTWI were both more frequent in athletes with identified cardiac disease (Table 4). The normalization of PTWI during exercise was more frequent in athletes without cardiac disease, with the localization of PTWI and ethnicity having no impact on the cardiac disease prevalence.
|Parameters||Cardiac Disease(n=69)||No Evidence of Cardiac Disease(n=86)||P|
|Age, y||30.0 [21.0–41.0]||26.0 [20.0–36.0]||0.09|
|Males||66 (95.6%)||83 (96.5%)||0.78|
|White||41 (59.4%)||44 (51.1%)||0.52|
|Afro-Caribbean||26 (37.7%)||38 (44.2%)|
|West-Asian||2 (2.9%)||4 (4.7%)|
|Training level (h/week)||8.5 [5.0–12.0]||12.0 [8.0–12.0]||0.07|
|Familial history||7 (10.1%)||2 (2.3%)||0.04|
|Systolic murmur||7 (10.1%)||9 (10.5%)||0.95|
|Left atrial hypertrophy||23 (33.3%)||22 (25.6%)||0.44|
|Abnormal Q wave||11 (15.9%)||6 (7.0%)||0.07|
|ST depression||32 (46.4%)||16 (18.6%)||0.0002|
|Sokolow index, mm||35.0 [28.0–42.0]||39.0 [30.0–45.0]||0.11|
|Exercise (n=141)PTWI normalization||39/56 (69.6%)||59/68 (86.7%)||0.013|
|All precordium||7 (10.1%)||6 (7%)||0.31|
|V1–V4||3 (4.3%)||7 (8.1%)||0.48|
|Lateral Leads||9 (13%)||14 (16.3%)||0.34|
|V5–V6||5 (7.2%)||11 (12.8%)||0.26|
|I–AVL + V5–V6||4 (5.8%)||3 (3.5%)||0.49|
|II– III– AVF||3 (4.3%)||4 (4.7%)||0.93|
|II–III–AVF + V5–V6||47(68.1%)||53 (61.6%)||0.40|
|II–III-aVF+ V1–V3||0||1 (1.2%)||0.26|
|I–aVL +V1–V3||0||1 (1.2%)||0.26|
This study aimed to prospectively determine the prevalence of cardiac pathology in athletes presenting with PTWI, and to examine the efficacy of including CMR in the battery of further examinations. Our data demonstrate that from 155 athletes presenting with PTWI, 44.5% demonstrate a serious cardiac pathology associated with sudden cardiac death (primarily HCM). CMR significantly increases the diagnostic capability of disease identification, especially in those athletes presenting with a normal echocardiogram. Finally, our data demonstrate that all athletes presenting with PTWI must be followed up annually before medical clearance for competitive sport can be given, because 5 athletes (7.2% of all positive cases) expressed disease after initially presenting with normal examination.
Prevalence of Cardiac Disease in Athletes Presenting With PTWI
The prevalence of PTWI observed in this study is similar to previously reported figures.16,26 It has been clearly demonstrated that in whites, PTWI prevalence (2% to 3%) is no different between athletes and nonathletes,27 but in Afro-Caribbean individuals, the prevalence of PTWI is higher in athletes than nonathletes.16
Our results reaffirm that marked PTWI is associated with a high prevalence of cardiac pathologies that are associated with conditions that may predispose athletes to SCD.9 Although our prevalence of disease is slightly higher than previously reported (45% versus 36%),9 in keeping with the majority of studies, HCM was our most common identified pathology (81% of all cases). Accordingly, all athletes with disease were excluded from competitive sports as recommended.13
Importance of Annual Cardiovascular Follow-Up
The present study did not observe PTWI normalization during follow-up as previously reported.9 Our data demonstrate the importance of annual follow-up, because almost 6% athletes who presented with PTWI but normal secondary investigations in initial examination later went onto develop clear pathology during follow-up.
However, in line with previous recommendations,9,14 it is unreasonable to disqualify 55% of athletes presenting PTWI but demonstrating normal secondary investigations. In the case of an asymptomatic athlete with PTWI but normal detailed cardiac evaluation and no family history of hereditary cardiac disease, we recommend unrestricted participation in competitive sports. Accordingly, we would inform and educate the athlete regarding the development of symptoms, and place under yearly cardiac evaluation. Further, we propose a systematic cardiac examination with 12-lead ECG and echocardiography of first-degree relatives (>10 years of age).
Efficacy of Using CMR in Athletes With PTWI
Although the prevalence of an abnormal TTE (24%) was similar to previously published data for athletes presenting with PTWI,9 initial TTE missed 46% of all diagnosed pathological cases. CMR provided a diagnosis in 88% of all cardiomyopathies and. importantly, established disease in 30% suspicious TTE and corrected 16.5% of TTE initially considered normal.
Previously, in conjunction with an ECG, echocardiography was considered the standard noninvasive diagnostic test for HCM. The diffuse nature of the disease pattern in HCM, however, limits the usefulness of echocardiography, which often fails to adequately visualize the anterolateral free wall and apex. The distribution of hypertrophy in HCM is often asymmetrical; consequently, subtle segmental areas of hypertrophy may be missed on echocardiography. In particular CMR is vital for assessment of apical hypertrophy and assessment of the anterolateral free wall.23,28 Thus, CMR is the reference standard imaging modality for the assessment of ventricular volumes, function, mass, and tissue characterization (eg, myocardial fibrosis) and in our opinion must be included in the work-up at athletes presenting with marked PTWI with normal echocardiographic examinations.
Clinical Value of the Other Examination Modalities
Positive family history rates were significantly higher in athletes diagnosed with a cardiac disease (P=0.04) than athletes presenting a normal hearts, demonstrating the importance of ascertaining such details. Sixteen athletes presented a systolic murmur on physical examination, from which 7 were diagnosed with HCM. Exercise testing and 24hr ECG Holter were abnormal in 12% and 18% of athletes, respectively with proven cardiac disease. Importantly, PTWI normalization during exercise was observed in 79% of the population studied, 87% and 70% of the athletes, respectively without and with cardiac disease. Thus, PTWI normalization during exercise cannot be used as a criterion of benignity.
Algorithm for Evaluating Athletes With PTWI
The Cost of Identifying Pathology
The cost-effectiveness of the entire ECG screening program is not within the scope of this study. However, because of the current debate concerning the cost-effectiveness of ECG screening in athletes,29 we calculated the cost-effectiveness using France medical reimbursement costs for the 155 athlete presenting with PTWI. It cost $1839 USD per athlete to identify cardiac disease, and $2620 USD per athlete when annual follow-up costs are included.
We acknowledge the absence of a gold standard test to diagnose HCM in athletes.24 Despite this, however, we used the latest ESC criteria for diagnosing and managing individuals with HCM. Although the presence of LGE is an important diagnostic feature supporting pathology, its absence does not exclude pathology. Nevertheless, our data support CMR as part of the routine work-up in athletes presenting with PTWI. Genetic testing was not provided for financial reasons. However, in an athlete with an overt cardiomyopathy, the yield of mutation identification is variable according to the disease: 50% to 70% in HCM and ≈40% in ARVC. Failure to identify a recognized mutation does not exclude the diagnosis of a cardiomyopathy or ion channelopathy for 3 important reasons: (1) not all genetic regions are assessed, (2) current technology is not able to detect some forms of mutation (intronic cryptic splice sites, large genomic rearrangements, etc), and (3) a similar phenotype may possibly develop without a specific genetic constitution. Finally, complementary CV screening of first-degree relatives was not possible in the majority of athletes because of the international nature of origin, feasibly explaining the lower than expected family history incidence of HCM.
In conclusion, PTWI was associated with cardiac pathology in 45% of athletes, with HCM the most common cardiac disease identified. Furthermore, CMR is paramount to increase the diagnostic capability to identify pathology even in the presence of a normal echocardiogram. Although automatic disqualification is unwarranted, all athletes presenting with PTWI must be followed up annually before medical clearance for competitive sport can be provided.
We thank N. Endjah, J.L. Foulgoc, and S. Caudmont for their help in data collection.
Sources of Funding
This study has been partly supported with a grant from
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Although rare, the observation of pathological T-wave inversion (PTWI) on the resting 12-Lead ECG of an asymptomatic athlete is one of the most serious sports cardiology issues. Indeed, PTWI is observed in several cardiac diseases related to sudden death in athletes. In the absence of documented pathology on secondary investigation, competitive sport may be authorized. Consequently, the true nature of PTWI in an asymptomatic athlete is not yet clearly defined or understood. This prospective study examined a large group of asymptomatic athletes (n=155), all presenting with PTWI. Athletes were well phenotyped with echocardiography and cardiac magnetic resonance (CMR), and were routinely followed up for a number of years. A diagnosis of cardiac disease was established in 45% of athletes, with hypertrophic cardiomyopathy (81%) the most common pathology. Once considered the gold standard secondary investigation, echocardiography missed a diagnosis of pathology in 35% of PTWI athletes, who were subsequently identified with disease on CMR imaging. This result supports CMR’s mandatory inclusion in the workup of athletes presenting with PTWI in case of normal echocardiography. Finally, this study also establishes the clear role for annual cardiovascular follow-up, because 7% of athletes initially granted authorization to play competitive sports later went on to develop cardiac pathology in subsequent years.