The role of imaging in the prevention of sudden cardiac death in sports cardiology

Cardiomyopathy

Cardiomyopathies are the leading cause of SCD in young athletes. Long-lasting ET promotes electrical, structural and functional adaptations of the heart that, in their most marked expression, can overlap with mild phenotypes of cardiomyopathies. Multimodality imaging plays a key role in this clinical conundrum as well as in risk stratification and monitoring patients with a cardiomyopathy who exercise on a regular basis. For adult athletes, an annual evaluation, usually alternating CMR and TTE, is recommended [1]. In adolescents and young individuals and in patients with high-risk genetic variants, this evaluation should be performed every six months [1].

The hypertrophic left ventricle

ET can promote an increase of the left ventricular wall thickness (LVWT). However, athletes rarely exceed the upper limit of normality established for the general population. Age, race, sex and sport discipline influence LVWT. Adult Black men who practice sports that combine volume and pressure overload (e.g., canoeing) exhibit the greatest LVWT values [2,3]. An LVWT ranging between 13-16 mm is considered to be the grey zone of overlap between physiological adaptations and the mild hypertrophic cardiomyopathy (HCM) phenotype. Echocardiography can establish the differential diagnosis of both entities with high sensitivity. Generally, when left ventricular hypertrophy (LVH) is the result of long-lasting ET, it should be accompanied by a concomitant LV dilatation, while athletes with HCM show a non-dilated LV in the vast majority of cases. In addition, physiological LVH usually shows homogeneous distribution while LVH in HCM patients is typically asymmetric [4]. An abnormal diastolic function constitutes a red flag for pathological LVH; however, in early phases of HCM expression, the E/A ratio can be normal [4]. In these cases, the evaluation of e’ velocity by tissue Doppler imaging has been demonstrated to be a better tool for identifying a subclinical impairment of LV diastolic function [5]. Finally, global LV systolic function is typically preserved in mild HCM. However, using speckle tracking echocardiography (STE) to evaluate the LV systolic function enables early identification of mechanical dispersion and an impaired LV contractile reserve, both being early signs of pathological LVH [5]. When an HCM diagnosis is confirmed, echocardiography is essential for risk stratification since it facilitates the assessment of the LV outflow tract gradient (both at rest and during exercise), the LVWT and the left atrial (LA) diameter [1].

CMR is the gold standard imaging technique for cardiac morphology and its functional evaluation, and it can also help to identify features that are suggestive of an early stage HCM, such as myocardial crypts, elongation of the anterior mitral valve leaflet or apically displaced papillary muscles [6]. Additionally, late gadolinium enhancement (LGE) sequences allow tissue characterisation. The presence of LGE would suggest pathological HCM; however, it may be absent in the early stages of HCM. When LGE is present, a patchy, intramyocardial pattern is the most common which corresponds with macroscopical fibrosis. The higher the percentage of fibrosis, the worse the prognosis given, the greater the risk of developing arrhythmic events. According to the latest 2023 ESC Guidelines for the management of cardiomyopathies [7], extensive LGE (>15%) favours the implantation of a prophylactic implantable cardioverter-defibrillator after shared decision-making. Furthermore, CMR can assess other features associated with high risk such as:  high values of extracellular volume (assessed by T1-mapping sequences), a reduced LV ejection fraction (<50%) and the presence of an apical pseudoaneurysm [6].

The dilated left ventricle

A mild/moderate dilatation of the left ventricle (LV) is commonly observed in athletes whose activities expose them to higher volumes of aerobic ET, such as endurance athletes [2]. This physiological LV dilatation should coexist with a proportional right ventricular (RV) and biatrial dilatation. In athletes, LV diastolic function is normal or supranormal and no wall motion abnormalities should be present [8]. However, in highly-trained athletes with a pronounced LV dilatation, global LV systolic function can be slightly reduced [8,9]. In such cases, exercise imaging techniques are indicated for the assessment of LV systolic function during exercise; with an impaired LV contractile reserve favouring a pathological over a physiological LV dilatation [8].

Regarding CMR, LGE sequences do not specifically help to establish the differential diagnosis between physiological LV remodelling and mild DCM since neither are expected to present extensive LGE. When pathological LGE is present, its pattern is essential for determining DCM aetiology. A subendocardial or transmural LGE pattern following a coronary vascular territory is associated with ischaemic heart disease, while a subepicardial LGE pattern without oedema is suggestive of previous myocarditis. Additionally, a mesocardiac LGE pattern in the basal interventricular septum is not associated with a specific aetiology, but it has been linked to poor prognosis [10]. These LGE pathological patterns should be differentiated from the LGE patterns documented in healthy individuals and from those found more frequently in highly-trained athletes, which are characterised by a small focus of LGE in the inferior intraventricular insertion; this has not been associated with worse cardiac remodelling nor with a worse prognosis [11].

Finally, LGE assessment has a pivotal role in risk stratification. LGE represents myocardial fibrosis, which, in turn, constitutes an arrhythmogenic substrate; as such, its presence and extension confers a higher risk while its absence is considered a predictor of good prognosis, regardless of LV ejection fraction [7].

Table 1. The role of the multimodality imaging in the diagnosis and risk stratification of cardiomyopathies.

TTE (Transthoracic Echocardiography):

• HCM (Hypertrophic Cardiomyopathy):
• Asymmetric LVH (Left Ventricular Hypertrophy)
• Abnormal diastolic function (reduced e’ velocity, early impairment)
• Mechanical dispersion of LV contraction
• Impaired LV contractile reserve
• DCM (Dilated Cardiomyopathy):
• Unbalanced LV dilatation
• LV systolic or diastolic dysfunction
• Impaired LV contractile reserve
• ARVC (Arrhythmogenic Right Ventricular Cardiomyopathy):
• Disproportional dilation of RVOT (Right Ventricular Outflow Tract) over the inflow
• Unbalanced RV dilation
• Mechanical dispersion of RV contraction

CMR (Cardiac Magnetic Resonance):

• HCM:
• Myocardial crypts, elongation of mitral leaflets, or apically displaced papillary muscles
• LGE (Late Gadolinium Enhancement) – patchy, intramyocardial pattern
• High extracellular volume
• Reduced LVEF (<50%)
• Apical pseudoaneurysm
• DCM:
• LGE pattern
• Insertion point (athlete’s heart)
• Subendocardial transmural (ischemia)
• Subepicardial (myocarditis)
• Mesocardial at basal septum (poor prognosis)
• ARVC:
• Akinetic or dyskinetic areas, and global dysfunction
• Presence of fibrofatty tissue and/or
• Presence of LGE

ARVC: arrhythmogenic right ventricular cardiomyopathy; CMR: cardiac magnetic resonance; DCM: dilated cardiomyopathy; HCM: hypertrophic cardiomyopathy; LGE: late gadolinium enhancement; LV: left ventricle; LVEF: left ventricular ejection fraction; LVH: left ventricular hypertrophy; RV: right ventricle; RVOT: right ventricle outflow tract; TTE: transthoracic echocardiography

Coronary artery disease

Coronary artery disease (CAD) is the main underlying cause of SCD in professional athletes.  In asymptomatic athletes with high cardiovascular risk, CAD should be ruled out. Maximal exercise testing should be in the first evaluation. When its results are equivocal, functional imaging techniques are indicated (exercise echocardiogram [ESE] or SPECT) [16].  If the latter are borderline or uninterpretable and the athlete is symptomatic or has positive CAD history, other structural or functional imaging techniques are recommended (cardiac computed tomography [CCT] or magnetic resonance [MR] angiography) [16].

In our experience, ESE is a first-line diagnostic test, widely available, low-cost, non-invasive, with no radiation involved. It evaluates ischaemia based on the global and segmental contractile reserve combined with haemodynamic, clinical and electrocardiographic parameters [17].  Its main limitations are the operator's experience and the acoustic window quality. Depending on availability and local experience, other alternatives to ESE would be SPECT or nuclear perfusion techniques (preferably with exercise rather than pharmacological stress) [16,17].

Modern CCT with multiple detectors and gated-ECG allow us to obtain an accurate definition of the coronary anatomy in a few seconds with a very low dose of radiation, especially in athletes who often have low heart rates [17,18]. CCT has a high negative predictive value. When a significant atheromatous plaque is identified, CCT enables its characterisation, thereby evaluating the associated risk and facilitating a potential treatment plan [18]. Additionally, aortic, pericardial diseases and coronary anatomical variants such as a coronary bridge can be ruled out during the same procedure.

Stress CMR is another recognised technique for detecting inducible myocardial ischaemia, and, with the use of coronary perfusion protocols (either with vasodilator drugs or with exercise), to assess ischaemic extension [19]. Moreover, CMR is able to characterise myocardial tissue, identifying an ischaemic myocardial scar and its extension. CMR, in addition to its diagnostic role, plays a major role in risk stratification and exercise prescription in athletes with known CAD [2].  

Aortopathy

Vigorous ET increases parietal tension in the aorta, which can result in remodelling. Previous meta-analyses in athletes <35 years of age have shown slightly greater aortic root diameters compared with sedentary controls. However, the aortic diameters in young athletes rarely exceed >40 mm in men and >34 mm in women. In professional athletes, recent studies suggest a higher prevalence of aortic dilation (21% >40 mm) as compared to age- and sex-matched sedentary controls with an equivalent cardiovascular risk factor burden. Nevertheless, it is unknown whether this mild dilation confers a greater risk of an aortic event [22].

Once a dilated aorta is documented, the risk of rupture should be assessed individually. It should be taken into account that hereditary thoracic aortic disease (HTAD) – Marfan syndrome being the most frequent – bicuspid aortic valve (BAV), a positive family history of dissection or SCD, high blood pressure and larger aortic diameters and strenuous strength exercise confer greater risk [1,23].

Thoracic aortic dilatation is generally asymptomatic and may go unnoticed on physical examination and/or on the ECG. It may debut as an acute aortic syndrome, which is a rare, but is a confirmed cause of SCD in athletes [1]. Imaging techniques therefore become essential in this clinical scenario.

TTE is the most routinely used imaging technique for diagnosis and follow-up. It provides a correct measurement of the aortic root and the proximal ascending aorta, assessing the presence of pathological flows in the aortic arch and, on the other hand, the functionality of the aortic valve [17]. Its main disadvantage is not being able to fully assess the aorta [17].

A global baseline assessment of the aorta, a precise measurement of the maximum diameter, location of the aneurysmal segment and characteristics of its wall can be done with magnetic resonance imaging (MRI) or computed tomography (CT). MRI is generally preferred over CT because of the risk of cumulative radiation exposure; this is especially true for young people who need serial follow-up [23,24]. CT angiography should be considered in case of MRI contraindication and/or prior planning of a surgical or percutaneous intervention.

All patients with an HTAD should undergo at least yearly imaging of the ascending aorta with TTE or MRI, depending on the case. In athletes with BAV or tricuspid valve (TAV) and a non-dilated aorta (<40 mm), follow-up every 2-3 years with TTE is recommended [1,24]. In athletes with BAV or TAV with diameters between 40-45 mm, the frequency of TTE may be either every 1 or 2 years depending on rate of growth [23]. An MRI may also be considered as part of the initial study or in case of discordant measurements by TTE. For patients with an aortic diameter ≥45 mm, a baseline MRI is recommended, along with annual TTE or even more frequently in cases of accelerated growth [24].

Valvulopathy

Bicuspid aortic valve (BAV)

BAV is the most prevalent genetic valve disease both in the general population and in athletes (0.5-2.0%). Although still controversial, the available evidence suggests that the progression of BAV occurs independently of sports practice [25,26].

Athletes with BAV may present stenosis or insufficiency and its management is similar to that of tricuspid valve disease [1].  When the valvular dysfunction is mild or absent, BAV may go unnoticed during physical examination. ETT is the first-line technique, allowing for an evaluation of the valve morphology and for the presence of potentially associated coronary anomalies to be ruled out [27].

On the other hand, BAV is associated with a small, but increased risk for ascending aortic aneurysm or dissection, and therefore with SCD.  As for BAV-associated valvular dysfunction, the impact of ET in aortic dilation is unclear. A single study comparing elite athletes with BAV, non-athletes with BAV and athletes with TAV showed no impact of athletic status on the aortic growth rate. However, studies with larger populations and longer follow-ups are needed to confirm this statement. ETT is again the first-line imaging technique for this scenario, as it allows the evaluation or aortic diameters and to discard BAV-associated aortic coarctation [2]. Aortic MRI and CT complement aortopathy evaluation- as described in the previous section.

Aortic stenosis

Aortic stenosis is a well-known cause of exercise-related sudden cardiac death, but is responsible for fewer than 4% of events in young athletes [1]. Decreased exercise tolerance, dyspnoea on exertion, or exercise-induced angina in an athlete with a systolic murmur should make us suspect this valvular disease.

The most common aetiology in the elderly population is degenerative, but in young individuals, the presence of an underlying congenital pathology such as BAV must be ruled out [28]. Echocardiography is the first-line technique for its diagnosis. It provides quantification of the stenosis severity, ventricular function and myocardial thickness as well as an evaluation of the underlying mechanism of the stenosis.

In individuals affected by moderate aortic stenosis who are asymptomatic and have a normal haemodynamic response, the evaluation of the aortic mean gradient during exercise by exercise echocardiography has an additional prognostic role; an increase of more than 20 mmHg is independently associated with a higher risk of adverse events during follow-up [29].  

On the other hand, in special cases, in which the information from the TTE is inconclusive or additional information is needed for an accurate diagnosis or to decide the best therapeutic strategy, non-invasive multimodal imaging can help us. The use of CCT is especially useful, as it is the complementary technique of choice to assess valve anatomy and calcification and to evaluate the characteristics of the annulus, aortic root, entire aorta and the aortoiliac vascular axis, allowing, as well, for the evaluation of the coronary arteries, especially in patients with a low probability of coronary artery disease [30].

Finally, CMR provides tissue characterisation identifying myocardial fibrosis and has also a promising role in the detection of subclinical cardiomyopathy through the use of myocardial T1 mapping and extracellular volume quantification in those patients who have not yet developed macroscopic fibrosis. All these parameters have prognostic implications and are promising tools for determining the optimal time to treat an asymptomatic patient with preserved ventricular systolic function and severe aortic stenosis [30].

For asymptomatic individuals with a mild aortic stenosis in which the ejection fraction is preserved, the haemodynamic response to exercise is normal, and who have no arrhythmias, these individuals can compete in all sports and participate in intense aerobic and strength training if it is their desire. Individuals with moderate aortic stenosis can perform low-to-moderate intensity exercise while those with severe stenosis should be restricted to low-intensity exercise and skill sports (golf, table tennis, etc.) [1]. 

Mitral valve prolapse

Mitral valve prolapse (MVP) is a common valvular disease in the general population (1.0-3.0%). It is caused by a myxomatous thickening of the leaflets. Diagnosis is made by TTE in which displacement >2 mm of one or both leaflets beyond the annular plane within the atrium in late systole is found [1]. In addition, TTE can help monitor the progression of mitral insufficiency, its volumetric and structural impact on the LV, and the development of pulmonary hypertension [1]. In cases in which there is doubt in grading the severity and/or in which symptoms are discordant, ESE is especially useful since it allows us to see the changes in regurgitant flow and pulmonary systolic pressure at maximum effort [30].

Generally, athletes with MVP have an excellent long-term prognosis. However, although uncommon, a malignant phenotype associated with life-threatening ventricular arrhythmias (VA) [31,32] has been identified. Recent studies using TTE and CMR have found morphological characteristics associated with this phenotype, regardless of MR severity or LV remodelling. These include bileaflet prolapse, mitral annular disjunction and superior displacement of papillary muscles (PM) [31,32].

It is believed that these alterations generate mechanical tension in the inferolateral myocardial wall and in the PM, which can cause mechanical dispersion (double peak strain in STE by TTE) and replacement myocardial fibrosis (demonstrated by LGE-CMR) which may be a possible mechanism for a life-threatening VA [31,32].

Likewise, in athletes with MVP the initial evaluation should include a comprehensive TTE, maximal exercise test and 24-hour ECG monitoring. If any VA, morphological risk feature and/or T-wave inversion on the ECG is identified, CMR is recommended to complete an SCD risk assessment [1]. 

Conclusion

A preparticipation cardiovascular evaluation (PPCE) is an efficient tool for identifying athletes with an underlying cardiac disease in which vigorous exercise training can act as a trigger of sudden cardiac death (SCD). The initial PPCE includes a detailed medical history, a complete physical examination and a resting 12-lead electrocardiogram. When this evaluation yields positive results, multimodality imaging then plays a pivotal role in confirming the diagnosis or excluding pathology. In most clinical scenarios, a transthoracic echocardiogram should be considered for first-line imaging followed by either cardiac magnetic resonance or cardiac computed tomography according to the suspected diagnosis. Moreover, imaging plays a major role in risk stratification and monitoring athletes with cardiac diseases.