Abnormal electrocardiographic findings in athletes: recognising changes suggestive of cardiomyopathy (onderdeel reeks ECG bundel, deel 1 (3a) van dit artikel)

Introduction

The cardiomyopathies are a diverse group of heart muscle diseases that are defined and subdivided in clinical practice by different structural and functional characteristics. As a family of related diseases, the cardiomyopathies are the leading cause of sudden cardiac death (SCD) in young competitive athletes.^1–3 Athletes with an underlying cardiomyopathy may present with disease-related symptoms or may be asymptomatic and thus only identified by abnormal testing during pre-participation screening. Although a definitive diagnosis may require extensive evaluation by a cardiovascular specialist, the 12-lead ECG is commonly abnormal among athletes with an underlying cardiomyopathy. Therefore, it is of paramount importance that clinicians responsible for ECG interpretation in athletes be familiar with key findings associated with underlying diseases of the heart muscle. This paper will review the principal ECG findings associated with the most common forms of cardiomyopathy relevant to the care of the young athlete. Initial testing for further evaluation of abnormal ECG findings is also presented.

Distinguishing normal from abnormal

A challenge in the use of ECG for screening or diagnostic evaluations in athletes is the ability to accurately differentiate findings suggestive of a potentially lethal cardiovascular disorder from benign physiological adaptations occurring as the result of regular and sustained intensive training (ie, athlete’s heart). Several reports have outlined ECG criteria intended to distinguish normal ECG findings in athletes from ECG abnormalities requiring additional evaluation.^4–9 On 13–14 February 2012, an international group of experts in sports cardiology and sports medicine convened in Seattle, Washington, to define contemporary standards for ECG interpretation in athletes. The objective of the meeting was to help physicians distinguish normal ECG alterations in athletes from abnormal ECG findings that require additional evaluation for conditions that predispose to SCD.¹⁰ A review of normal ECG findings in athletes is presented separately.¹¹ In this paper, abnormal ECG findings are presented relative to the most common cardiomyopathies associated with SCD in athletes: hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM) and left-ventricular non-compaction (LVNC). Table 1 summarises a list of abnormal ECG findings unrelated to athletic training that may suggest the presence of an underlying cardiomyopathy and should trigger additional evaluation in an athlete.

Hypertrophic cardiomyopathy

HCM is a genetic disease of the heart muscle. It is characterised by ventricular hypertrophy in the absence of a recognisable cause such as aortic valve disease or hypertension. A common pattern of hypertrophy in HCM is an asymmetric septal hypertrophy where the interventricular septum is thicker than the rest of the left ventricle. However, many other patterns of pathological hypertrophy are consistent with HCM such as apical hypertrophy, concentric hypertrophy and proximal septal hypertrophy. Poor ventricular compliance (diastolic dysfunction) is characteristic, along with microvascular dysfunction which contribute to ischaemia during exercise. Some patients have dynamic left ventricular (LV) outflow tract obstruction caused by the combination of hypertrophy and abnormalities of the mitral valve which leads to systolic anterior motion of the anterior leaflet. However, only about 25% of patients with HCM have a murmur from LV outflow tract obstruction during resting examination.¹² Symptoms of HCM include chest pain, syncope and exercise intolerance, but for many persons the disease can be asymptomatic and SCD may be the clinical presentation of the disease.¹³ Fibrosis of the heart muscle is characteristic and may underlie ventricular arrhythmias and sudden death. On histopathological analysis, disorganised cellular architecture with cardiac myocyte disarray is a hallmark feature.¹²

Prevalence

HCM is among the most common inherited cardiovascular disorders and may occur in 1 : 500 adults and at equal prevalence in men and women.¹² However, the reported prevalence of HCM in competitive athletes is apparently lower, approximately 1 in 1000 to 1 in 1500 athletes.^{3 14} HCMis inherited primarily as autosomal dominant with variable penetrance, and morphological expression of HCM may appear in childhood but typically develops in early adolescence through young adulthood. This may contribute to the lower prevalence of HCMfound in younger athletes.

Contribution as a cause of SCD

In most case series, HCM is among the most common causes of SCD in young athletes. In the USA, HCM accounts for approximately one-third of identified causes of SCD in athletes, and in the UK HCM represents 11% of cases.^{1 15} HCM is a less common cause of sudden death in other populations. In US military personnel, HCM accounted for only 6% of SCD, and in the US general population (less than 35 years old) only 5% of cases of sudden cardiac arrest were attributed to HCM.^{16 17}

Diagnostic criteria

HCM can be diagnosed by ECG in combination with echocardiography or cardiac MRI. An LV wall thickness of 1.5 cm or greater is normally required to make the diagnosis, but marked asymmetry with lower absolute wall thickness measurement is also compatible with HCM. The upper limit of normal wall thickness in most echocardiography laboratories is 1.2 cm. A ‘grey area’ is defined between 1.2 and 1.5 cm. In borderline cases, other features favouring a diagnosis of HCM include impaired diastolic function, small LV cavity size, LV wall thickness asymmetry, mitral valve pathology (leaflet redundancy and systolic anterior motion) and the presence of myocardial fibrosis (late gadolinium enhancement) on cardiac MRI.¹⁸

Abnormal ECG findings in HCM

Over 90% of patients with HCM will have an abnormal ECG.^19–21 ECG abnormalities include T wave inversion (TWI), ST segment depression, pathological Q waves, conduction delay, left-axis deviation (LAD) and left atrial enlargement (LAE).

T wave inversion

TWI in the lateral or inferolateral leads is seen commonly in HCM (figures 1–3). In a series of asymptomatic patients ≤35 years old with HCM confirmed by cardiac MRI, 62% exhibited TWI.²¹ Similarly, in patients with a positive HCM genetic test and overt morphological HCM, 54% demonstrate TWI.²² In black patients with HCM, TWI occurs more commonly in the lateral leads (77%) and less frequently in the inferior leads (2%).²³ Abnormal TWI is defined as >1 mm in depth in two or more leads V2–V6, II and aVF, or I and aVL (excludes leads III, aVR and V1). Deep TWI in the mid-precordial to lateral precordial leads (V4–V6) should raise the possibility of apical HCM.

In healthy athletes, TWI in the lateral or inferior leads is uncommon. TWI beyond V2 is a rare abnormality found in only 0.1% of Caucasian adolescent athletes older than 16 years.²⁴ In a college athletic population of mixed ethnicity, TWI in the lateral or inferolateral leads is reported in 2% of athletes.25 In Caucasian elite athletes, the prevalence of TWI in the lateral or inferior leads is also about 2%.²⁶ However, TWI is more common in black athletes of African-Caribbean descent (hereto referred to as ‘black/African’ athletes). TWI in the lateral or inferior leads is reported in 8–10% of black/African athletes.^{23 27}

Repolarisation variant in black/African athletes

TWI in the anterior precordial leads should be distinguished from TWI in the lateral or inferior leads in black/African athletes. TWI in the anterior precordial leads may be part of a normal variant pattern of repolarisation in black/African athletes consisting of convex (‘dome’ shaped) ST segment elevation followed by TWI in V1–V4 (figure 4). On the basis of current data, TWI preceded by ST segment elevation are present in the anterior precordial leads in up to 13% of black/African athletes and do not require further assessment in the absence of symptoms, positive family history or abnormal physical examination. ^{23 27} However, TWI in the lateral or inferolateral leads (V5–V6, I and aVL, II and aVF), regardless of ethnicity, is considered abnormal and requires additional testing to rule out HCM (figures 1–3).

Juvenile pattern of TWI

TWI in the anterior precordial leads in younger, prepubertal athletes often reflects a persistent juvenile pattern and requires careful interpretation. In Caucasian adolescent athletes, anterior precordial TWI extending beyond V2 was present in 1.2% of athletes <16 years but only 0.1% of athletes ≥16 years.²⁴ In a study of Italian adolescent athletes, incomplete pubertal development was an independent predictor for right precordial TWI.²⁸ The prevalence of right precordial TWI decreased significantly with increasing age, 8.4% in children <14 years of age versus 1.7% in those ≥14 years.²⁸

Biphasic T waves

Biphasic Twaves create a challenge and currently there is no consensus regarding the definition of TWI when a large positive deflection precedes a negative portion below the isoelectric line. If the negative portion of the Twave is >1 mm in depth in two or more leads (excluding leads III, aVR, and V1), it is reasonable to consider this pattern as abnormal until more data are obtained.

ST segment depression

ST segment depression is a common abnormality in HCM but extremely rare in otherwise healthy athletes, making it a concerning indicator of disease if identified on an athlete’s ECG. ST segment depression is reported in 46–50% of patients with HCM, but in <1% of apparently healthy athletes or adolescents undergoing ECG screening.^{9 22–25} Any degree of ST depression beyond 0.5 mm in two or more leads is significant and requires further investigation for cardiomyopathy (figures 1 and 2).

Pathological Q waves

Q waves have been defined in different ways in different populations. In patients with overt HCM, pathological Q waves are reported in 32–42% of patients.^{19 22} In one series of asymptomatic patients with HCM, 42% demonstrated pathological Q waves.²¹ The consensus of this group is to define Q waves for HCM as >3mm in depth or >40 ms in duration in at least two leads (excluding leads III and aVR; figure 5). This detects HCM with a sensitivity of 35% and a specificity of 95% in patients with preclinical HCM based on molecular genetic diagnosis.²⁹

Intraventricular conduction delay

Left bundle branch block (LBBB) is an abnormal finding detected in 2% of patients with HCM but not reported in screening populations of athletes or adolescents.^{9 22 25} LBBB pattern with a QRS duration of 120 ms or greater should prompt further evaluation (figure 6). Right bundle branch block (RBBB) is found more commonly in HCM than in athletes but the frequency of incomplete and complete RBBB in athletes is felt to limit its differentiating value.^{23 30} The significance of a non-specific intraventricular conduction delay (IVCD) with normal QRS morphology is uncertain. However, marked nonspecific IVCD >140 ms is considered abnormal and should prompt further evaluation.

Left axis deviation

LAD, defined as −30° to −90°, is present in almost 12% of HCM patients but less than 1% of athletes (figure 7).^{9 23 25} LAD can be a secondary marker for pathological LV hypertrophy (LVH) and if present warrants additional evaluation.

Left atrial enlargement

ECG findings suggestive of LAE have been defined in different ways. Overall, LAE on ECG is present in approximately 10–21% of HCM patients but has been reported in up to 44% of black patients with HCM (figure 8).21–23 LAE is defined as a prolonged P wave duration of >120 ms in leads I or II with negative portion of the P wave ≥1 mm in depth and ≥40 ms in duration in lead V1. LAE on ECG is an uncommon finding in athletes and should prompt additional investigation.

Increased QRS voltage in athletes and HCM

The isolated presence of high QRS voltages fulfilling voltage criterion for LVH is regarded as a normal finding in athletes related to physiological increases in cardiac chamber size and/or wall thickness and does not in itself require additional evaluation. ^{5 6} As expected, voltage criteria for LVH also are commonly identified in individuals with HCM. However, the presence of isolated increased QRS voltage in the absence of other ECG abnormalities is uncommon and present in <2% of individuals with the disease.¹⁹ Several studies have evaluated athletes and young adults with isolated increased QRS voltage using echocardiography or cardiac MRI and none had HCM.24 26 31–33 Therefore, isolated increased QRS voltage on the ECG in the absence of other abnormalities in an asymptomatic athlete with a negative family history is not a reliable indicator of HCM and does not require further evaluation. Co-existing ECG abnormalities such as TWI, ST segment depression, pathological Q waves, IVCD, LAD or LAE should be investigated by additional testing.

Evaluation of suspected HCM

If HCM is suspected based on ECG abnormalities, evaluation of LV morphology and function is required.³⁴ Echocardiography provides assessment of LV cavity size and wall thickness, systolic and diastolic function and valvular structure and function, and is the first test of choice under most circumstances. HCM can be diagnosed when wall thickness is ≥1.5 cm with normal or small LV cavity size in the absence of other causes capable of causing myocardial hypertrophy. Diastolic dysfunction, mitral valve pathology and LVoutflow tracts obstruction are other findings that support the diagnosis of HCM.

However, echocardiographic quality is variable based on numerous factors, including operator proficiency and patient acoustic windows, and may have limited ability to detect hypertrophy of the anterolateral LV wall and apex (figure 9).35

Cardiac MRI provides superior assessment of myocardial hypertrophy and may demonstrate late gadolinium enhancement which is a non-specific marker suggesting myocardial fibrosis. Cardiac MRI should be considered when echocardiography is insufficient to assess all myocardial segments or when myocardial hypertrophy falls into the ‘grey zone’ between 1.2 and 1.5 cm. Cardiac MRI is recommended for markedly abnormal ECGs suggestive of apical HCM, specifically ECGs with deep TWI and/or ST depression in the inferolateral leads (V4–V6, I, aVL, II and aVF), in which echocardiography often does not provide an adequate assessment of the LV apex or inferior septum (figures 1–3).

A common clinical dilemma is the detection of myocardial hypertrophy in an athlete in which the hypertrophy may be due to physiological adaptation to exercise. Differentiating athlete’s heart from HCM requires careful clinical evaluation by an experienced provider.^36–38 Cardiac MRI, cardiopulmonary exercise testing and Holter monitoring should be considered. Findings suggestive of HCM include the presence of unusual patterns of hypertrophy with substantial differences in wall thickness of the LV segments, normal or reduced LV cavity size, extreme LAE, diastolic dysfunction, family history of HCM or SCD, below normal peak oxygen consumption (peak VO2), and the presence of ventricular arrhythmias. When diagnostic uncertainty remains, genetic testing and/or a period of deconditioning followed by reassessment to document regression (or lack thereof) of exercise-induced LVH may be considered.

Long-term follow-up of markedly abnormal ECGs

Highly trained athletes occasionally present markedly abnormal ECG patterns instinctively suggesting the presence of a cardiomyopathy.39 40 Such abnormal ECGs raise the question of differentiating between the initial, subtle expression of cardiac disease or the extreme but innocent ECG expression of the ‘athlete’s heart’.^{26 41 42} Investigators researched the clinical outcomes of 81 athletes presenting initially with markedly abnormal repolarisation patterns in the absence of detectable cardiac abnormalities.⁴³ After an average 9-year follow-up, a new diagnosis of cardiomyopathy was made in five athletes (6%), including three with HCM, one with ARVC and one with DCM.⁴³ Two athletes experienced adverse events (0.3% per year), including one cardiac arrest from HCM and one sudden death related to ARVC.⁴³ Markedly abnormal ECGs, therefore, may represent the initial expression of cardiomyopathy, preceding by many years the phenotypic or morphological expression of structural heart disease.

Athletes presenting with distinctly abnormal ECGs (ie, deep TWI in the lateral leads) and no evidence of structural heart disease after a thorough work-up may be permitted to participate in competitive athletics. However, these athletes should undergo serial clinical evaluation on an annual basis, even in the absence of symptoms, including repeat imaging tests such as echocardiography and/or cardiac MRI to evaluate for the development of cardiomyopathy.

Competing interests None.
Provenance and peer review Commissioned; internally peer reviewed.