Preventing sudden cardiac death in young athletes – A perspective from the United States

Abstract

Sudden cardiac death in young athletes is a rare, but devastating complication of several clinically silent conditions which can become unmasked during periods of intense physical activity. Prevention of sudden cardiac death starts with robust screening to allow the early identification of at risk individuals and the implementation of preventive strategies. The specific approach to screening (history and physical, with or without pre-participation electrocardiograms) varies across the globe with some notable differences between that used in Europe and the United States. The rationale for this variation is complex, but can be linked to the differences in risk factor prevalence, the healthcare infrastructure, and the capacity to identify and triage at risk individuals in a cost-effective manner. Beyond knowing the differences in the approaches to screening, establishing strategies that work (including novel techniques) and those that can be implemented in a successful and sustainable manner are key.

Few things are as dramatic as witnessing an athlete's sudden cardiac death (SCD) during a sporting event. While extremely rare, when these traumatic events occur, they are widely publicized, highly scrutinized, and reignite the robust debate around the need for enhanced strategies to keep athletes safe while taking part in sports.

SCD is defined as the unexpected death within one hour after the onset of symptoms due to a cardiac cause. SCD may be the first clinical manifestation of several previously undiagnosed lethal cardiac conditions that provide a substrate for fatal arrhythmias triggered during periods of intense physical activity [1]. Physical stress might also produce the milieu for a catastrophic event such as aortic rupture, as is the case of an undiagnosed aortopathy.

In this issue of the journal, Bronzetti et al. present an impassioned call to screen young athletes for multiple potentially fatal, but asymptomatic cardiac conditions via transthoracic echocardiography (TTE). This recommendation builds on the existing screening program in Italy, which utilizes a history & physical examination and baseline 12- lead electrocardiogram (ECG) and was sparked by discovering a previously undiagnosed, but potentially lethal coronary anomaly via TTE. The authors argue that expanding athlete screening to include TTE could save lives. However, could such an approach be adopted in the United States (US)?

1. An extremely rare, but devastating event

It is estimated that as many as 55% of all high school students in the US participate in sports [2], with a varied reported prevalence of SCD among young athletes (age < 35 years) based on the population studied and the method used to capture these unfortunate events. However, according to one large study of National Collegiate Athletic Association (NCAA) athletes, the incidence was 1 in 53,703 athlete years [3].

Conceptually, the most common causes of SCD in young athletes fall into one of five categories (Table 1) [4]. These include cardiomyopathies (hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular non-compaction, and dilated cardiomyopathy), ion channelopathies (Long QT syndrome, short QT syndrome, Brugada syndrome, and polymorphic ventricular tachycardia), valvulopathies, anomalous coronary arteries, and aortopathies [4]. Notably, for a sizeable number of cases, no specific cause is identified.

Table 1.

Common causes of sudden cardiac death in competitive athletes.^a

Disorders of myocardium/cardiac structure

Hypertrophic cardiomyopathy

Arrhythmic right ventricular cardiomyopathy

Familial/idiopathic dilated cardiomyopathy

Left ventricular noncompaction cardiomyopathy

Toxic cardiomyopathy (alcohol, illicit anabolic steroids, etc.)

Acute and subacute myocarditis

Simple and complex congenital heart disease

Disorders of the cardiac electrical system

Ventricular pre-excitation/Wolff-Parkinson-White syndrome

Congenital long QT syndrome

Catecholaminergic polymorphic ventricular tachycardia

Idiopathic ventricular tachycardia

Commotio cordis

Disorders of coronary circulation

Congenital anomalies of coronary arterial origin and course

Acquired atherosclerotic disease

Disorders of heart valves

Bicuspid aortic valve (with ≥ moderate stenosis ± aortopathy

Pulmonic stenosis (with ≥ moderate stenosis)

Mitral valve prolapse (with corollary arrhythmogenicity)

Disorders of the aorta

Bicuspid aortic valve aortopathy

Idiopathic aortopathy/thoracic aortic aneurysm

Marfan syndrome

Loeys- Dietz syndrome

Turner syndrome

Ehlers-Danlos vascular type (IV)

^aReprinted from Journal of the American Society of Echocardiography, Vol 33, Issue 5, Aaron L. Baggish, Robert W. Battle, Timothy A. Beaver, William L. Border, Pamela S. Douglas, Christopher M. Kramer, Matthew W. Martinez, Jennifer H. Mercandetti, Dermot Phelan, Tamanna K. Singh, Rory B. Weiner, Eric Williamson, Recommendations on the Use of Multimodality Cardiovascular Imaging in Young Adult Competitive Athletes: A Report from the American Society of Echocardiography in Collaboration with the Society of Cardiovascular Computed Tomography and the Society for Cardiovascular Magnetic Resonance, Pages No. 523-549, Copyright (2020), with permission from Elsevier.

However, these risk factors are not universal and vary based on the setting, genetics, and demographic makeup of that location. For instance, in Italy, arrhythmogenic right ventricular cardiomyopathy appears to be a dominant risk factor for SCD in young adults, compared to hypertrophic cardiomyopathy in the US [5], [6]. This variation in risk factor prevalence has important practical implications.

2. Prevention starts with risk identification through appropriate screening

Given the heterogeneous nature of sporting activities among young athletes, the various settings in which they take place, and the wide range of fitness levels of athletes, screening must be sensitive enough to detect disease without the drawback of excluding low-risk individuals from participating in sports. Additionally, screening must be able to detect inherent differences in the risk factors based on the population examined.

The American Heart Association (AHA) and the European Society of Cardiology (ESC) endorse pre-participation screening in athletes; however, there is disagreement about the best approach. The AHA supports a detailed History & Physical (H&P), which is inexpensive, but has poor sensitivity as most athletes are asymptomatic. Thus, the H&P only identifies a minority of those athletes at risk for SCD. The inclusion of the ECG (as recommended by the ESC) improves sensitivity for detecting serious cardiac disease. Still, it is associated with an unacceptably high false-positive (FP+) rate partly because of the overlap between the electrical manifestations of athletic training and the cardiomyopathies [7].

In a 2021 update to a 2012 policy statement, the American Academy of Pediatrics addressed this need for standardized and versatile screening, with an increased emphasis on the need for pre-participation evaluation [8]. In this recommendation, the responsibility for screening shifts to the purview of primary care providers (PCP), compared to a prior less stringent approach.

At the core of the screening process is the AHA 14-point screening tool, which assesses a number of historical factors (including symptoms such as syncope or chest discomfort and family history of predisposing cardiac conditions) and a physical examination focused on detecting findings suggestive of a heightened risk of SCD [9]. According to these recommendations, any abnormal findings during this screening evaluation should prompt referral to a cardiologist if deemed necessary by the PCP. If conditions that pose the young athlete at risk for SCD are identified, shared decision-making among the healthcare team, the athlete, and the family on discontinuation of competitive level sports participation should be considered. The latter point is supported by the AHA/American College of Cardiology (ACC) Scientific statement on the Eligibility and Disqualification Recommendations for Competitive Athletes with Cardiovascular Abnormalities [10].

A key concern raised about the AHA 14-point evaluation is its limited sensitivity. To determine a higher risk of cardiac events, a questionnaire study was conducted among 3620 student high school athletes, including 53% male athletes and 8% black athletes. Based on the results of the questionnaires, of which 45% were (-) and 55% were (+), a limited TTE was indicated in 1154 athletes. The ability for abnormalities that predispose young athletes to SCD to be detected by the AHA 14-point evaluation was poor compared to ECG (sensitivity 18.8% vs. 87.5% respectively). The accuracy of a screening tool to detect the conditions of a greater concern without unnecessary additional testing for FP(+) results is an important criterion in the evaluation of screening modalities and a measure used previously to criticize ECG screening [11].

Another concern beyond the limited sensitivity of the AHA 14-point evaluation is the non-universal uptake and implementation of this screening tool. For instance, at the national level, one study showed that as many as 20% of states did not use screening questionnaires aligned with prior AHA recommendations [12].

3. Enhancing screening via electrocardiography

As is the case in the US, screening via pre-participation evaluation H&P is standard practice in Europe. However, the screening recommendations by the ESC go a step further and propose the universal pre-participation screening with ECGs [13]. A central driving force behind this recommendation is the experience of the Italian national pre-participation screening program, which was found to be effective at reducing the incidence of SCD in young competitive athletes [14]. Via this program in the Veneto region in the North of Italy, over a 26-year period, the annual incidence of SCD in young athletes decreased by 89%. However, it is worth noting that in Italy, the annual screening of competitive athletes for SCD is not merely a recommendation, but is required by national law [15]. So, why has this approach not been replicated in the US?

There is little question that ECGs vastly aid in screening young athletes for SCD. A meta-analysis by Harmon et al. showed that compared to H&P alone, adding ECGs to screening increased the sensitivity of detecting disorders suggestive of an increased risk for SCD [16]. Specifically, in this study, the sensitivity of ECG screening for detecting risk factors for SCD was 94% compared to 20% by history and 9% for physical examination alone. Despite its clear superiority over traditional screening, there are several arguments against widespread ECG screening.

One of the main arguments presented against the use of ECG screening is the perception that it is not a cost-effective strategy in the context of the US healthcare infrastructure. Based on data from the 20-year Italian experience, researchers extrapolated that the cost to establish a national pre-participation ECG screening program in the US would be astronomical [14], [17]. According to the authors, replicating the Italian ECG-based screening program in the US over a 20-year period would cost between $51to 69 billion, with a cost-per-life-saved ranging from $10.6 to 14.4 million.

On the other hand, a few real-world, large-scale ECG-based screening programs have been proven successful and cost-effective. One such screening program was conducted in Chicago, Illinois, under the Young Hearts for Life (YH4L) initiative [18]. In this program, over 32,000 high school students underwent ECG screening for causes of SCD. Of the screened individuals, 2.5% had abnormal findings that prompted further evaluation, with a projected cost per individual screened of $13.17 to $18.19. While the program was not designed to capture the number of lives saved or SCD events averted, the program was thought to be cost-effective.

However, financing similar ECG-based programs at the institutional level might prove cost-prohibitive, particularly in several traditionally underserved communities across the nation, where the existing budgets for sporting activities are extremely limited. One alternative would be to pass the cost on to the athletes themselves or their families. However, mandating such might result in drop-in sports participation rates, as the financial burden might be beyond what can be afforded by large segments of the population.

Beyond these points, another key unanswered question is whether detecting and removing asymptomatic young athletes found to have abnormalities on ECG from participating in sporting activities translates to the prevention of death, as the lethality of these conditions is not universal [19]. Based on this point and the limited evidence to suggest widespread screening with ECGs to be cost-effective and practical, current US guidelines, including those from the AHA and the ACC, do not recommend the use of widespread ECG screening of young athletes. They note, however, when affordable by institutions, ECG screening can be considered [10]. Beyond the guidelines, some sporting organizations in the US, such as US Rowing, have taken things further to stipulate ECG screening prior to participating in US Rowing events, an approach likely to be replicated by other sporting bodies [20].

4. Echocardiography as a next step

The call to action by Bronzetti et al. presents the integration of echocardiography as a potential next step in the screening for SCD in an environment where the infrastructure for such additional screening exists.

Echocardiography has many applications as an adjunct tool in the screening for SCD in competitive athletes (CA). There is very little ambiguity in the echocardiographic findings for bicuspid aortic valve (AV), aortopathy, valvular disease, pathologic cardiomyopathies, and congenital heart disease with a well-trained echocardiographer interpreting the studies. For example, echocardiograms in CA with ECGs suggestive of hypertrophic cardiomyopathy can appropriately guide further management. While not typically included by most echocardiography protocols in the US, attempting to definitively identify the origins of coronary arteries is possible and could supplement existing echocardiographic studies [21].

Many conditions, particularly hypertrophic cardiomyopathy or those with early stages of dilated cardiomyopathy, share findings that may be normal in athletes, requiring a cautious approach to differentiate these entities. An appreciation of the several normal echocardiographic variants in CA by the interpreting provider is critical. For instance, CA with adaptive changes relative to athleticism will have left ventricular (LV) cavity dilatation to accommodate training-related volume changes of 55 mm or greater (a finding in non-competitive athlete populations might suggest pathology). In this situation, the diastology of the LV will be normal, there will be no systolic anterior motion (SAM) of the anterior mitral valve leaflet, and the hypertrophy will reduce within three months of deconditioning [22].

However, a significant barrier to this approach in the US is whether the inclusion of TTE screening could be done cost-effectively.

Beyond monetary cost, several additional important considerations to this approach would need to be explored. For instance, it is unknown if the use of TTE screening would translate to actual lives saved. We do not know the incremental benefit of such an approach over the standardized questionnaire and ECG. Furthermore, the potential downstream consequences of a FP(+) (misinterpreted) TTE for a young CA may be immense. Given the paucity of data on this screening approach at the population level, further evaluation is warranted before including TTE as a component of the universal screening process.

In the US, the American Society of Echocardiography, in collaboration with the Society of Cardiovascular Computed Tomography and the Society of Cardiovascular Magnetic Resonance, have provided recommendations on the role of echocardiography in the evaluation of athletes [4]. While deemed a modality with several strengths in screening for SCD among young athletes (Table 2), important pitfalls exist that limit this screening tool and have been listed in these recommendations. These include several technical components of TTE, such as the inconsistent ability to visualize the proximal coronary arteries, definitively assess chamber geometry, and determine the presence of fibrosis, a substrate for ventricular arrhythmia. In their clinical algorithm, these guidelines suggest obtaining a TTE as a second step, based on the presence of abnormal findings on history & physical examination or pathologic findings on ECG (Fig. 1).

Table 2.

Comparative assessment of multimodality imaging in the case of competitive athletes.^a

Test attribute	TTE	CT	CMR
Cost	+++	++	+
Accessibility	+++	++	+
Portability	+++	+	+
Normative data in competitive athletes	+++	+	++
Ability to characterize LV morphology	++	+++	+++
Ability to characterize RV morphology	+	++	+++
Ability to characterize ventricular tissue composition	+	+	+++
Ability to define proximal coronary anatomy	+	+++	++
Ability to characterize LV systolic function	+++	++	++
Ability to characterize LV diastolic function	+++	+	+
Ability to characterize aortic morphology	++	+++	+++
Ability to characterize valve function and morphology	+++	++	++

+++. Excellent; ++, good; +, fair.

^aReprinted from Journal of the American Society of Echocardiography, Vol 33, Issue 5, Aaron L. Baggish, Robert W. Battle, Timothy A. Beaver, William L. Border, Pamela S. Douglas, Christopher M. Kramer, Matthew W. Martinez, Jennifer H. Mercandetti, Dermot Phelan, Tamanna K. Singh, Rory B. Weiner, Eric Williamson, Recommendations on the Use of Multimodality Cardiovascular Imaging in Young Adult Competitive Athletes: A Report from the American Society of Echocardiography in Collaboration with the Society of Cardiovascular Computed Tomography and the Society for Cardiovascular Magnetic Resonance, Pages No. 523-549, Copyright (2020), with permission from Elsevier.

Fig. 1.

Clinical algorithm for the application of multimodality imaging in the application of multimodality imaging in competitive athletes following pre-participation cardiovascular screening.^⁎

^⁎Reprinted from Journal of the American Society of Echocardiography, Vol 33, Issue 5, Aaron L. Baggish, Robert W. Battle, Timothy A. Beaver, William L. Border, Pamela S. Douglas, Christopher M. Kramer, Matthew W. Martinez, Jennifer H. Mercandetti, Dermot Phelan, Tamanna K. Singh, Rory B. Weiner, Eric Williamson, Recommendations on the Use of Multimodality Cardiovascular Imaging in Young Adult Competitive Athletes: A Report from the American Society of Echocardiography in Collaboration with the Society of Cardiovascular Computed Tomography and the Society for Cardiovascular Magnetic Resonance, Pages No. 523-549, Copyright (2020), with permission from Elsevier.

5. Potential way forward

As our knowledge surrounding SCD in young athletes continues to evolve, so too must the screening strategies we employ. It seems unjustified to continue emphasizing the use of a screening tool with poor performance, inconsistent application, and a low chance of identifying the majority of young athletes at risk of SCD. In light of these deficiencies to our existing screening program, we should first improve the screening process. Additionally, we must put greater emphasis on research and education to advance preventive strategies, improve screening tools, and develop a larger physician workforce capable of more effective CV screening, especially in high-risk athlete groups [10].

We must ensure universal uptake of standardized screening utilizing a team approach and an increased clinical capacity for additional evaluation when concerning findings are demonstrated. The team should be comprised of medical professionals with complementary expertise in sports medicine, cardiovascular (CV) subspecialists, and non-CV internal medicine specialists (Fig. 2) [4].

Fig. 2.

Overview of the clinical team approach to the assessment and management of competitive athletes with cardiovascular disease.^⁎

^⁎Reprinted from Journal of the American Society of Echocardiography, Vol 33, Issue 5, Aaron L. Baggish, Robert W. Battle, Timothy A. Beaver, William L. Border, Pamela S. Douglas, Christopher M. Kramer, Matthew W. Martinez, Jennifer H. Mercandetti, Dermot Phelan, Tamanna K. Singh, Rory B. Weiner, Eric Williamson, Recommendations on the Use of Multimodality Cardiovascular Imaging in Young Adult Competitive Athletes: A Report from the American Society of Echocardiography in Collaboration with the Society of Cardiovascular Computed Tomography and the Society for Cardiovascular Magnetic Resonance, Pages No. 523-549, Copyright (2020), with permission from Elsevier.

Furthermore, from a legislative standpoint, ensuring universal screening of athletes might be a worthwhile lesson from the Italian experience. Though this remains controversial, the AHA guideline leaders are advocating for legislation to mandate the use of the AHA 14-point screening tool during the well-child-care evaluations [23].

Once these issues are addressed, improving access and the cost-effectiveness of ECGs as a primary means of SCD screening might yield significant dividends. Continuing to use multimodality imaging (including TTE) as an adjunctive tool for the diagnosis, risk stratification, and exclusion of cardiovascular disease in high-risk CA seems most practical [4].

As became apparent during the management of the COVID-19 pandemic, we need to be flexible with our ability to listen to the science and adjust protocols to save lives. Most importantly, while the specific strategy employed in SCD screening might vary between the US clinicians and our Italian counterparts, we share a unified goal: keeping young athletes safe during sports.

Funding source

None.

Financial disclosures

Volgman: Research support: NIH IND Number 119127; NIH NINR R01NR018443; Novartis CTQJ230A12001. Consulting: MSD/Bayer Virtual Global Advisory Board Member, Bristol Myers Squibb Foundation Diverse Clinical Investigator Career Development Program (DCICDP), National Advisory Committee (NAC), Janssen Health Equity/Diversity Advisory Board. Stock ownership: Apple Inc. stock.

No other authors have no disclosures.

CRediT authorship contribution statement

Jamario Skeete: Writing – original draft, Writing – review & editing. Gatha Nair: Writing – review & editing. Henry D. Huang: Writing – review & editing. Annabelle Santos Volgman: Conceptualization, Writing – review & editing. Melissa Tracy: Writing – review & editing.

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Volgman: Research support: NIH IND Number 119127; NIH NINR R01NR018443; Novartis CTQJ230A12001. Consulting: MSD/Bayer Virtual Global Advisory Board Member, Bristol Myers Squibb Foundation Diverse Clinical Investigator Career Development Program (DCICDP), National Advisory Committee (NAC), Janssen Health Equity/Diversity Advisory Board. Stock ownership: Apple Inc. stock.