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Sudden Cardiac Death in Young Athletes
Advances in Pediatrics 60 (2013) 201–215
ADVANCES IN PEDIATRICS Sudden Cardiac Death in Young Athletes Mohammed Mortazavi, MDa,b,* a
Department of Pediatrics, UC Davis Medical Center, 2521 Stockton Boulevard, Sacramento, CA 95817, USA; bPediatric Sports Medicine, UC Davis Medical Center, 2805 J Street, Suite 300, Sacramento, CA 95817, USA
Keywords
Sudden cardiac death Hypertrophic cardiomyopathy Automated external defibrillator Sports medicine ECG Incidence Prevention
Key points
Incidence of sudden cardiac death (SCD) is now recognized to be several times higher than once believed based on recent epidemiologic data such as the 2012 study of National Collegiate Athletic Association athletes across the country, which suggests an incidence of 1 per 44,000 athlete deaths per year.
There are multiple causes of SCD in young athletes, with most attributed to hypertrophic cardiomyopathy.
Improving ECG and echocardiography (echo) technology, along with the advent of the cardiac MRI and genetic studies, provide physicians with multiple screening and diagnostic options to identify lethal cardiac disease.
Today, multiple treatment options exist for potentially lethal structural and arrhythmogenic cardiac disorders. With the medical therapy, surgical therapy, and genetic testing available, there can be many life years saved by identifying even one previously unidentified young athlete.
For the purposes of the general pediatrician, it is critical to identify at-risk patients in the office who may require an ECG or further work up. Identification of these patients is emphasized at the preparticipation examination, but should not be excluded to athletes participating in organized sports who require clearance.
INTRODUCTION The death of a young healthy athlete has always been an unimaginable shock to the communities that endure them. These young athletes are often considered the models of health and the pillars of our society. Thus, it is difficult *Department of Pediatrics, UC Davis Medical Center, Sacramento, CA. E-mail address: [email protected] 0065-3101/13/$ – see front matter http://dx.doi.org/10.1016/j.yapd.2013.04.015
Ó 2013 Elsevier Inc. All rights reserved.
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to accept how suddenly and tragically they can fall victim to underlying deadly heart conditions. With the increase in the recognition of these tragedies, many questions have arisen regarding the best prevention strategies of sudden cardiac death (SCD) in our young population. SCD in young athletes has drawn significant attention over the last three decades, in particular with the deaths of several high-profile athletes due to various underlying cardiac conditions. Research of SCD in the young athlete has blossomed recently. As a result, many questions regarding the approach to primary and secondary prevention of SCD have manifested. As recently as 30 years ago, SCD in young athletes under the age of 35 was thought to be an extremely rare phenomenon, one that was compared with the chance of being struck by lightning. However, with improving reporting methods, screening technology, and autopsy identification of such conditions, the recent literature suggests otherwise [1–3]. There are multiple causes of SCD in young athletes with the most attributed to hypertrophic cardiomyopathy (HCM) [1,4–9]. Other common causes of SCD include anomalous coronary arteries, arrhythmogenic right ventricular dysplasia (ARVD), commotio cordis, and channelopathies [4,9]. Although myocardial infarction is the number one cause of SCD across all ages, it is a relatively rare cause in the young athlete under the age of 35, accounting for less than 3% [2,4,9]. Improving ECG and echocardiography (echo) technology, along with the advent of the cardiac MRI and genetic studies, provide physicians with multiple screening options to identify lethal cardiac disease. Today, multiple treatment options also exist for potentially lethal structural and arrhythmogenic cardiac disorders. With the medical therapy, surgical therapy, and genetic testing available today there can be many life years saved by identifying even one previously unidentified young athlete. Recent studies in Italy and the United States suggest a higher incidence of silent, potentially lethal cardiac conditions than was previously believed [1–3,10]. As a result, demand for local ECG screening campaigns and even national screening programs has grown recently. As more screening programs continue to manifest, research continues to follow the efficacy and costeffectiveness of ECG screening. For the purposes of the general pediatrician, it is critical to identify at-risk patients in the office who may require an ECG or even further work up. Identification of these patients is emphasized at the preparticipation examination, but it should not be excluded to athletes participating in organized sports who require clearance. To identify anyone at risk for SCD, questions regarding types of activity and any symptoms during activity should be asked of all pediatric patients during regular physicals. Ultimately, identification of a single, silent diagnosis that can be treated is the reason we screen thousands. EPIDEMIOLOGY AND INCIDENCE Prevention of SCD first begins with understanding the real incidence of this phenomena, which has been quite a quandary when comparing epidemiologic
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data [1,2,4,9]. Although reporting of this phenomenon in the United States has improved with increasing media and Internet coverage, there is still a significant margin for underestimation when the general US population is considered. In contrast to our Italian counterparts, the United States does not have systemic mandatory reporting registry for SCD events. In Veneto Italy, Corrado and colleagues [2,3] have been following the trends of SCD in athletes under the age of 35 since the 1970s with an established mandatory reporting system. With the advantage of a socialized health care system that serves 95% of the population requiring mandatory reporting of all SCDs, the Italian incidence data has received much recognition [2,3]. The contrast between the Italian data and US incidence data was the source for much controversy and, ultimately, one of the key reasons for dismissing considerations of ECG screening programs in the United States through much of the 1980s and 1990s. Most SCD incidence data in the United States were produced by Maron and colleagues [9]. They reported incidence rates of SCD from 1980 to 2006 in all US athletes ages 12 to 39 in 38 different sports. They analyzed 1866 sudden deaths using media reporting registries. Their initial reports of SCD in the 1980s were exceedingly rare at less that 1 per 5000,000 deaths per athlete per year. However, this data showed a rise of about 6% per year to approximately 1 per 160,000 athlete deaths per year from 2000 to 2006 [9]. The question remained, was this a true dramatic increase in occurrence of this phenomena? Or was this a result of improved reporting with the advent of the Internet and improved media surveying. During this same period, the Italians were reporting the incidence of SCD in all persons 12 to 35 in Italy in a prospective observational study [3]. They followed trends of SCD using a mandatory socialized medicine registry along with media surveying data. This data showed several interesting trends: 1. Incidence of SCD was found to be 1 per 28,000 athlete deaths per year in 1980 before the advent of a national screening program using ECGs in Veneto, Italy. 2. Most of these deaths were due to HCM, ARVD, and anomalous coronaries. 3. This incidence was 1 per 100,000 deaths per year in nonathletes at that time, suggesting that athletic activity increases the risk for SCD by about threefold. 4. This incidence of SCD and, in particular, HCM was greatly reduced over time with the advent of ECG screening in 1980.
The discrepancy in incidence between the Italian and US data raises several questions. In particular, is there a significant lower incidence in the United States? Or is the US population not as well defined and thus SCD is underreported. One explanation has been that the primarily white Italian population cannot compared with the diverse US population, which includes many African American athletes. However, studies have shown that the incidence of SCD due to HCM is two to three times as high in African Americans when compared with whites [4–6,9]. HCM is also the leading cause of death in all young athletes in the United States [4–6,9]. So the question remained, if a study was done in the United States that looked at a defined population
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with a mandatory registry data, what would the results be? A more recent study done at the University of Washington by Harmon and colleagues [1] looking at incidence of SCD in the National Collegiate Athletic Association (NCAA) among all sports and across all divisions has provided insight on this question. Results showed that there was an overall incidence of 1 per 44,000 deaths per year in NCAA athletes between 2004 to 2008. This was a substantial difference with a threefold to sixfold higher incidence from previous large US studies. When this incidence is applied to the young athlete population in the United States, about 150 to 225 deaths per year can be approximated. Subgroup analysis showed that incidence was as high as 1 per 7,000 deaths per year in male African American athletes and as high as 1 per 3000 deaths per year in male African American division I basketball players [1]. Although the absolute number of deaths studied is still limited, ongoing data collection since 2008 in this well-defined NCAA population will provide much more insight on the most accurate incidence of this phenomenon in young American athletes [1]. The data from this study has certainly highlighted the potential benefit of ECG screening in these higher risk groups as primary prevention of SCD [1]. ECG screening programs for NCAA athletes are currently being investigated in a multi-institution study. CAUSES Sudden cardiac death in young athletes has multiple causes. By far the most common cause of death is HCM, which accounts for 33% to 50% of cases of SCD [4,9]. The second most common cause of SCD in the United States is coronary anomalies of heart, accounting for 17%. This is followed by myocarditis, accounting for 6%, and several other causes such as ARVD, aortic stenosis, dilated cardiomyopathy (DCM), long QT syndrome, and other channelopathies, each accounting for 2% to 5% of cases of SCD [4,9]. Congenital heart diseases, which have a rising incidence of surviving into adolescents and adulthood also only accounted for less than 3% of causes of SCD [4–6,9]. HCM deserves special attention given its drastically higher prevalence and often silent presentation before SCD. HCM is a heterogeneous autosomal dominant genetic condition with more than 12 known genotypes and various phenotypes [4,11,12]. It results in abnormal structure and architecture of the left ventricle. HCM can lead to lethal left ventricular outlet obstruction or arrhythmia, in particular with activity. Abnormal architecture of thickened disorganized myocytes can lead to areas that undergo chronic infarction and subsequent fibrosis. These areas then become ectopic foci for deadly arrhythmias such as ventricular fibrillation. There are multiple subtypes of HCM described based on area of hypertrophy including septal, basal, apical, and concentric [4,9,12–14]. It is estimated that the prevalence of HCM is 1 per 500 in the general population and that it is more common in males and African Americans [9,12,13]. Phenotypically it is usually a silent disease without any symptoms. However, it can become suddenly lethal in certain cases, with exercise as a known trigger. When there is suspicion on history or physical, the
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diagnosis is then confirmed by ECG, echo, and specialized cardiac imaging if necessary. Traumatic causes are typically not considered when discussing common causes of silent heart diseases causing SCD. Commotio cordis is a traumatic cause for SCD that deserves attention. Several studies have quoted up to 20% of all SCD in young athletes are due to this phenomenon [15]. Commotio cordis, meaning ‘‘agitation of the heart,’’ occurs after a timely blunt force to the chest, during the T wave ascent, which causes the heart to go into lethal ventricular fibrillation [15]. Although commotio cordis can occur at any age, the mean age is 13 with a propensity for younger athletes with less developed chest walls. Studies have found modest forces such as a baseball at 40 miles per hour from 40 feet away creating enough force to set a child’s heart into commotio cordis when hit in the precordial region during the ominous 40 m T wave ascent [15]. The sensitive zone of the precordium for induction of rhythm disturbances lies between the second and fourth rib to the left of the sternum. Commotio cordis is 90% lethal unless treated with an automated external defibrillator (AED) to defibrillate out of lethal rhythms back into sinus rhythm. AEDs can increase survival rates to 35% to 50% if administered in time, with some studies quoting survival rates of 90% to 100% when AED is administered within first minute [15]. RISK FACTORS Epidemiologic studies do show some general trends of risk factors for SCD among sport, sex, and race [1,4,9]. The highest risk sports for SCD are basketball, track, cross country, football, soccer, and swimming in descending order [9]. Lower intensity aerobic sports such as Bethesda class IA and IB sports are lowest risk for SCD, thus patients with many known potentially lethal heart diseases are restricted to these sports. Males have been shown to have an overall higher incidence of SCD than females and, in particular, a higher incidence of HCM. Traditionally, males were believed to have an 8 to 12 times higher incidence of SCD than females. However, recent studies that involve higher profile elite female athletes have suggested that males only have a 2 to 3 times higher risk for SCD [1]. In particular, SCD in female swimmers was noted to be of higher incidence than males [1]. This was postulated as perhaps a result of the higher incidence of long QT in females triggered by the dive reflex in swimmers [1,4,9]. ARVD has also been noted as more common in white athletes [2,3,9]. Based on studies in the United States, ARVD was found to be a relatively rare cause of SCD when compared with HCM, and almost exclusive to whites [9]. In current Italian studies, ARVD is the most common cause of SCD in their predominately white population [2,3]. This is in part because deaths due to HCM have been greatly reduced by their ECG screening program. Overall, the incidence of SCD in African American athletes has been noted to be about two to three times that of white athletes [1,9]. There is a considerable higher incidence of HCM in African Americans, which is likely the reason for their overall higher incidence of SCD [9].
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DIAGNOSIS AND PREVENTION Diagnosis of cardiac conditions that predispose one to SCD is often very challenging. However, with a good history and physical (H&P) one can determine those in need of further testing or workup. Although these are relatively rare diseases, they can have catastrophic consequences if undiagnosed. In general, screening is best when it is most sensitive to avoid missing any diagnoses. Trying to increase sensitivity can decrease the specificity of screening, resulting in the need to rule out more initial false positives with further testing. Further testing usually involves an echo, but may require stress testing, more advanced imaging, or genetic testing. The initial H&P will be the most critical place for general practitioners to identify any red flags that indicate need for further testing. In 2007, the American Heart Association (AHA) released their most recent statement on use of a 12-point H&P with the most critical questions for prevention of SCD (Table 1) [4]. Any positive findings on H&P should warrant an ECG and possible further workup depending on ECG results. Critical questions in the medical history include any personal history of cardiac symptoms (eg, chest pain, presyncope, syncope, excessive dyspnea on exertion) during exercise. If any of these symptoms are noted, it is critical to ask follow-up questions regarding quality, severity, and timing of symptoms. In particular, the specific timing of symptoms with respect to exercise is critical to discern. If they are reported during exercise, it is important to determine if symptoms were during exercise versus before or after exercise when one would be more likely to have normal physiologic symptoms. Any history of true syncopal episodes during exercise should be discerned and referred to a cardiologist. Additional history of a previously recognized murmur or hypertension should also trigger further questioning and an ECG to rule out the possibility of underlying heart disease. Family history of SCD or disability from heart disease in a close relative under the age of 50 should also initiate an ECG. Any relative with a known, potentially lethal genetic cardiac disorder such as HCM, DCM, long QT, or Marfan disease should also trigger further workup with an ECG. Physical examination findings of a pathologic heart murmur, decreased femoral pulses, stigmata of Marfan syndrome, hypertension, or asymmetric blood pressures should also trigger further workup with ECG and cardiology referral. ECG In 2007, the AHA stance on the use of systematic ECG screening in the prevention of SCD was that this endeavor is currently too costly and not feasible as a national program [4]. They also noted potential medical legal and ethical concerns with disqualification and clearance of athletes as major barriers to having such a program [4]. Despite the Italian experience and International Olympic Committee’s stance, which recommends an H&P and ECG for every athlete, the AHA comments that the international community cannot be generalized to the US population. In the United States, there are over 10 million athletes and no infrastructure to support screening initiatives such as those that have
History and examination
Findings
Actions
Personal History
Chest pain or discomfort, presyncope during activity Syncope during activity Excessive and unexplained dyspnea or fatigue during
ECG ECG, cardiology referral ECG, rule out exercise induced asthma (pulmonary function test, exercise challenge) ECG ECG, repeat blood pressure
History of heart murmur High blood pressure Family History
Physical Examination
Any relatives who died of SCD before age 50 Close relative under age 50 with disability from heart disease Specific knowledge of certain cardiac conditions in family members: hypertrophic or DCM, long QT syndrome, Marfan syndrome, or clinically important arrhythmias Heart murmur Diminished or asymmetric femoral pulses Physical stigmata of Marfan syndrome Asymmetric of elevated (>140/90 mm Hg) blood pressure
ECG, cardiology referral ECG ECG, cardiology referral
ECG, cardiology referral pathologic murmurs ECG, cardiology referral ECG, cardiology referral ECG, cardiology referral
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Table 1 12-Point recommended participation H&P by the American Heart Association for prevention and screening of SCD in young athletes
for concerning for further imaging for further imaging for further imaging
Data from Maron BJ, Thompson PD, Ackerman MJ, et al. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 2007;115:1643–455.
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grown successful in Italy and Europe [4]. Despite this, many leagues, community programs, and volunteer organizations in the United States have began to offer screening ECGs to athletes. Several studies of ECG screening in college athletes have suggested it to be a feasible and cost-effective life-saving screening tool [1,16]. The original model for ECG screening in Italy has been shown to reduce SCD by 89% over the last 30 years [2,3]. Their initiative was spearheaded by primary care sports medicine physicians who are the work force for reading all screening ECGs. They work in conjunction with cardiologists to evaluate all athletes deemed high risk by an abnormal ECG screen. Starting with very sensitive criteria in the 1980s, they have developed more specific criteria over time and have significantly reduced the false positive rate to less than 20% [2,3]. The University of Washington has been screening NCAA athletes with only a reported 10% to 12% false positive rate, using sports medicine physicians to lead the initiative to screen all athletes with ECGs [17]. A 2010 study at Harvard using echo confirmation found three athletes with potentially lethal heart disease out of 500 screened, two of which (HCM, myocarditis) required the ECG to make the diagnosis [16]. This study reported a false positive rate of 17% with screening ECGs [16]. A recent study done in Colorado that performed H&P along with screening ECG for 1000 high school athletes ages 13 to 18 found two potentially lethal diagnoses (long QT and WolffParkinson-White [WPW] syndrome) based solely on the ECG screens. ECGs were read by a pediatric sports medicine primary care physician (PCP) before a pediatric cardiologist and a false positive rate of about 11% was noted from the initial PCP reads. Many ECG screening programs are now using PCPs or primary care sports physicians in primary prevention of SCD. These programs all follow different models but, in general, PCPs are used for first-line screening of ECGs using very sensitive guidelines [2,3,17,18] Any positive findings are sent to cardiologists for review and determination if a cardiology consult is warranted based on the ECG findings. This approach may lead to a large number of false positives that require cardiology read or consults with further testing required. However, the literature shows the false positive rates have dramatically decreased over the last 20 years with the use of more specific ECG interpretation guidelines [18]. With continuing research, the first-line screening criteria initially established by Corrado and colleagues in Italy over three decades ago has grown more specific while maintaining an expected high sensitivity [2,3,11,18]. ECG INTERPRETATION The ECG criteria can be systematically reviewed by any PCP who is comfortable reading basic ECGs. Beginning with rate, rhythm, and axis, the PCP should evaluate for tachycardia, bradycardia, arrhythmia, and axis deviations. Heart rate (HR) in a young athlete is expected to be 60 to 100, but can be as low as 30 in the conditioned athlete [11,19,20]. True bradycardia with HR less than 30 should be assessed for heart block or sick sinus syndrome. Tachycardia is less common in athletes and thus the age of athlete must be considered as
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well as any recent activity or cause for anxiety during pulse examination. If true tachycardia is repeatedly noted, superventricular tachycardia (SVT) should be considered. With SVT, HR is typically greater than 220 and there is no beat-to-beat variability. Arrhythmias to screen for include atrial fibrillation, atrial flutter, and any other ventricular arrhythmias. Greater than two premature ventricular contractions (PVCs) per ECG strip should also warrant further investigation with repeat ECG or cardiology consult. True axis deviation may suggest several pathologic findings such as right ventricular hypertrophy (RVH) or HCM. Using the more refined criteria, evaluation for any right axis deviation greater than 115 and left axis deviation greater than 30 would be cause for concern and cardiologist consult [18]. Assessment of axis deviation in the pediatric athlete must also consider the age of the athlete. Rightward axis deviation, which is normal at birth, transitions to leftward axis in adolescence and adulthood depending on age. Thus, some younger athletes may still have normal transitioning right axis deviation. Other factors that can cause pathologic axis deviation include chronic pulmonary disease or systemic hypertension, in which case further cardiology workup is warranted [18]. Next, a review of ECG for any abnormal atrial abnormalities should be done. This involves an evaluation of the P waves, which represent atrial contraction. Any P wave greater than 2.5 mV in amplitude in any lead is concerning for right atrial enlargement. Left atrial enlargement manifests with prolonged total duration of the P wave greater than 120 ms, or a negative deflection of the P wave in V1, V2 that is both greater than 1 mV in amplitude and greater than 40 ms in duration. Atrial abnormalities are often found to be nonpathologic, but can be related to RVH, HCM, and increased pulmonary resistance, and should warrant a cardiology consult. After reviewing the morphology of the P wave, the PR interval should be calculated to rule out any findings of heart block. First-degree heart block or a PR interval of 200 to 300 ms is considered to be a normal physiologic manifestation of increased vagal tone seen in athlete’s heart (AH) [11,12,19]. PR intervals greater than 300, progression of the PR interval, dropped P waves, or P-QRS dissociation are concerning for second and third degree heart block that should be further evaluated. A thorough evaluation of the QRS complex should be done starting with the depth and width of Q waves. Abnormally wide or deep Q waves should rise concern and trigger further workup. Any Q waves deeper than 3 mV or longer than 40 ms in any leads other than leads III, AVR, AVL, and V1 should initiate a cardiology consult. Evaluation of QRS complex starts by ruling out any up-slanting QRS complex with short PR interval, usually less than 120 ms, that would be consistent with delta waves seen in WPW syndrome. Evaluation of the QRS complex should also involve assessment for any bundle branch blocks, or interventricular conduction delays (IVCDs), defined by a QRS interval greater than 120 ms. Right and left bundle branch blocks can be identified based on their specific morphology in V1 (RSR9 , QS) and increased QRS interval greater than 120 ms. Most IVCDs in asymptomatic
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patients will lead to normal imaging and workups. However, associations with HCM, atrial septal defects, and Chagas disease in endemic countries exist [18]. Thus, IVCD should be taken seriously and cardiology consulted for possible further workup. Most computer interpretations will be more accurate than standard measurements for QRS duration and should be reviewed carefully along with visual inspection for any specific bundle branch block morphologies. The R and S wave amplitudes should be measured to determine if there are any abnormally large amplitude concerning for RVH or left ventricular hypertrophy (LVH). In general, large R wave amplitudes in anterior leads such as V1 can be a sign of RVH. Specific recommendations include assessing for any R wave greater than 7 mm in V1, R/S ratio greater than 1, or the sum of the R wave in V1 and S in V5 or V6 that is greater than 10.5 mV [18]. These findings may warrant further workup for RVH, especially in athletes older than 30 years of age [18]. Any of the above findings for RVH plus right atrial enlargement, right axis deviation greater than 115, or T wave inversion in V2 or V3 are specifically concerning for pathologic RVH in the young athlete under the age of 30 and warrant further workup [18]. LVH typically presents with prominent R waves now in the lateral leads V4 to V6 or deep S waves in the anterior leads. There are several different methods of assessing for LVH including the Sokolow-Lyon Index (SLI) and Cornell voltage criteria. No one method is perfectly sensitive or specific, but use of combined criteria can improve sensitivity and specificity. Using the SLI, the sum of S in V1 and R in V5 or V6 greater than 35 mV is considered isolated LVH. This correlates with echo measurements of greater than 10 to 12 mm of concentric left ventricular myocardial wall thickness [11]. Isolated LVH is a very common finding in conditioned athletes secondary to physiologic hypertrophy and remodeling of the heart muscle in response to exercise. When findings of LVH are isolated without any other associated abnormalities, such as Q wave abnormalities, lateral lead T wave inversions, or ST changes, no further workup is necessary [18]. There have been several postulations that perhaps LVH can be a precursor to HCM; however, there is no evidence in the literature to suggest this. There is no study done to date that has followed a group of young adolescents with LVH to determine if any develop pathologic heart disease such as HCM. ST CHANGES OR T WAVES ST segment changes may be associated with HCM and ARVD due to areas of infarction secondary to abnormal myocyte and vessel architecture. Any ST segment depression greater than 0.5 mV below the isoelectric line in the lateral leads, AVL, or lead I are concerning and should warrant further workup. ST segment depression greater than 1 mV in any lead should also warrant further workup. ST changes secondary to coronary artery disease and myocardial infarction are rare in the young athlete. However, other silent lethal cardiac diseases such as HCM and ARVD can present with ST depression without
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associated hypertrophy patterns on ECG [3,5,9,18]. ST segment elevation in lateral leads V3 to V6 that is less than 0.5 mV is commonly seen due to early repolarization in conditioned athletes and is a very common finding in AH [11,12]. Early repolarization may or may not be associated with LVH also commonly seen conditioned athletes. Recent epidemiologic studies have shown prevalence of greater than 50% in conditioned adult athletes [11,12,19]. Physiologic early repolarization can be confused with the abnormal J wave seen Brugada type 1 pattern, which resembles ST elevation from the isoelectric point. However, Brugada pattern is seen in V1 to V3, and the characteristic J wave usually has ST elevation significantly greater than 0.5 mV. Any ST segment elevation in V1 to V3 should be evaluated closely for Brugada syndrome and warrant cardiac consultation. Postexcitation potentials or epsilon waves are also seen in leads V1 to V3 with a post-QRS hump pattern seen before the T wave. Epsilon waves are usually associated with a T wave inversion. This pattern has been associated with ARVD and other cardiac pathologic conditions and deserves further workup [18]. T WAVE INVERSIONS OR QT CHANGES T wave inversion in certain leads can be concerning ECG findings. T wave inversions have been noted in 2% to 4% of the adult athlete population without any cardiac disease [18]. It is important to recognize that T wave inversions in anterior leads V1, AVR, and III can be normal. In females and children, T wave inversion in V1 to V3 is typically normal. T wave inversions in athletes under 18 were noted in the anterior leads in up to 20% of athletes [18]. Studies looking at T wave inversions in African Americans have noted an incidence of 14% and normal T wave inversion patterns in V2 to V4 [18]. However, if significant T wave inversions greater than 1 mV are noted in any of the lateral or inferior leads further workup is warranted. The European Consensus Statement has suggested any T wave inversions greater than 2 mV in two or more contiguous leads should be considered as a very significant abnormality requiring definite workup [18]. QT INTERVALS QT interval changes should be closely measured and reviewed for any prolonged or short QT syndromes. Criteria suggest QTc measurements in lead 2 or V5 using standard measurement of QT interval divided by square root of preceding RR interval. Any QTc measure less than 340 ms is considered short QT and requires referral. More commonly, long QT syndrome is seen defined by QTc greater than 470 in males and greater than 480 in females [18]. A QTc of 440 to 470 is considered borderline and should be followed with a repeat ECG or a stress ECG. Long QT syndrome is well defined with several different genotypes isolated and strongly associated with SCD risk. Long QT type 1 is the most common genotype, with exercise as the main known trigger for SCD. Genetic testing for the QT genotype can help determine appropriate therapy and prevention strategies as well as confirm
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diagnosis. These include treatments with beta blockers, activity restriction, and implantable cardioverter-defibrillators (ICDs). Family genetic testing can also help determine if other high-risk family members have the syndrome and may require treatment. ECG CRITERIA FOR AH AH is a phenomenon that must be well understood in the interpretation of screening ECGs and prevention of SCD. The recognition of this phenomenon is not to identify uniquely conditioned hearts, but instead to prevent mistaking them for abnormal hearts. ECG criteria for AH include any one or combination of the following: 1. 2. 3. 4. 5.
Bradycardia First-degree atrioventricular block Incomplete right bundle branch block LVH Early repolarization.
These findings in a young athlete should be expected and considered as normal. Identification of ECG findings of AH is critical to recognize to prevent many false positives. ECG criteria for AH is seen in up to 80% of elite adult athletes and 60% of pediatric athletes [4,12,19]. Comfort with routine recognition of these findings is important for the PCP to prevent a large influx of unnecessary referrals and workups. FURTHER WORKUP Patients with concerning findings on H&P or ECG often will need to be referred for further cardiac workup. In general, any of the concerning ECG findings on (Table 2) should be reviewed with a cardiologist to determined whether a referral is needed [18]. Findings consistent with AH (Table 3) are normal and require no further workup if indeed ECG is limited to these isolated normal physiologic training changes. Despite ECG findings, any concerning symptoms such as true syncope, palpitations, or chest pain during exercise should be referred. The additional workup by a cardiologist will depend on the diagnosis of suspicion. In general, this will involve an ECG, echo, and other possible workup. Stress ECGs may be required to make certain diagnoses such as catecholaminergic polymorphic ventricular tachycardia (CPVT), which is a lethal arrhythmia that is solely exercise induced. Cardiac MRI provides very detailed imaging of cardiac anatomy, which can be very helpful in multiple diagnoses including HCM, ARVD, and anomalous coronaries. Cardiac MRI can be performed dynamically to assess function, or with gadolinium to highlight abnormal cardiac tissue and fibrosis. Genetic studies available for disorders such as HCM and long QT are very helpful in characterizing the disease for optimum treatment when phenotypes are gene positive. Family genetic testing is important in all gene positive patients to help identify others that may have been affected by the disease.
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Table 2 Abnormal ECG findings Assessment
Abnormality
ECG criteria
Rate
P waves
Sick sinus syndrome SVT PVCs Ventricular arrhythmias Atrial fibrillation Atrial flutter Left axis deviation Right axis deviation Left atrial enlargement
PR intervals
Right atrial enlargement Second-degree heart block
Q waves
Third-degree heart block Abnormal Q waves
QRS
Delta wave
ST changes
Left bundle branch block Right bundle branch block IVCD RVH ST segment depression
HR <30 HR >220, no beat-to-beat variability 2 or more per ECG — — — More leftward than 30 More rightward than 115 P wave >120 ms OR P wave with negative deflection in V1, V2 with >1 mV, >40 ms P wave >2.5 mm in any lead PR >300 ms Prolonged PR intervals, Dropped P waves P-QRS wave dissociation (>3 mV) OR (>40 ms) in any lead except III, aVR, aVL, or V1 Up-slanting QRS (delta waves) and PR <120 ms QRS >120 ms in V1 with QS wave pattern QRS >120 ms in V1 with RSR9 pattern QRS duration >120 ms in any lead R wave >7 mm in V1 or R/S ratio >1 >0.5 mm below isoelectric line before T wave in leads V4, V5, V6, I, aVL or >1 mV in any lead Epsilon waves with T wave inversion V1 to V3 J-wave pattern in any of V1, V2, or V3 >1 mV in any lead other than V1, III, aVR (except V2, V3 in females) >470 ms males, >480 ms females <340 ms
Rhythm
Axis
Postexcitation potentials
T waves QT abnormalities
Brugada type 1 pattern T wave inversion Long QT Short QT
MEDICAL PREVENTION Diagnosis of potentially lethal cardiac disease is critical to initiating medical management to prevent a sudden cardiac event or death. Depending on the cause, multitude medical options exist that are usually initiated and managed by a cardiologist. With the diagnosis of HCM, medications such as beta blockers may be started. Activity restriction to class IA sports per the Bethesda classification is recommended. ICDs are placed in some higher risk patients or patients with a history of near death events. A recent high-profile professional soccer player in Europe with the diagnosis of HCM did not comply with activity restriction recommendations and returned to soccer after treatment with beta blockers and an ICD. He had a subsequent event that would have likely resulted in death; however, while lying pulseless, his ICD shocked and revived him.
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Table 3 Normal ECG findings of AH Finding
ECG criteria
Sinus bradycardia First-degree heart block Incomplete RBBB Early repolarization Isolated LVH
HR 30–60 beats per minute PR 200–300 ms V1 RSR9 morphology with QRS 100–120 ms ST elevation <0.5 mV in V3–6 S in V1 and R in V5 or V6 35 mV
Depending on area and severity of cardiac hypertrophy, a surgical myomectomy can be performed to prevent outlet obstructions. When known ectopic foci of arrhythmias exist, such as in WPW or certain cases of HCM or ARVD, ablation therapy can be used to ablate these foci. Channelopathies, such as Brugada syndrome, CPVT, and long QT syndrome, can be treated with beta blockage and anti-arrhythmic agents depending on specific type diagnosed with genetic testing. Primary prevention of SCD begins with a thorough, well-informed H&P following the AHA 12-point questionnaire, followed by ECG screening for any high-risk athletes. Primary prevention also involves awareness and education of both the athletic and medical communities. The cost and effort spent on primary prevention to save a single life must be understood by all parties involved to have a successful screening program. Secondary prevention involves being prepared to prevent a death when an event occurs. Too often, silent lethal cardiac conditions manifest for the first time as lethal arrhythmias or outlet obstructions leading to asystole. Cardiopulmonary resuscitation is the most helpful and applicable skill that can help directly save lives in these situations. The availability of AED devices can be critical in situations with shockable rhythms. Most deaths caused by HCM and commotio cordis are due to lethal ventricular fibrillation that can be shocked back to sinus rhythm by an AED. Most modern AEDs are very easy to use with simple three-step directions. Education about the function, use, and potential life-saving capabilities of AEDs are critical for community providers and officials. Funding and availability for AEDs has greatly increased in recent years and, today, many facilities such as schools and gyms will have an AED available. Healthcare professionals covering any sporting event should check with officials on the location of the AED and be prepared for its use, if necessary. References [1] Harmon KG, Asif IM, Klossner D, et al. Incidence of sudden cardiac death in National Collegiate Athletic Association athletes. Circulation 2011;123:1594–600. [2] Corrado D, Pelliccia A, Heidbuchel H, et al. Recommendations for interpretation of 12-lead electrocardiogram in the athlete. Eur Heart J 2010;31:243–59. [3] Corrado D, Michieli P, Basso C, et al. How to screen athletes for cardiovascular diseases. Cardiol Clin 2007;25:391–7, v–vi.
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[4] Maron BJ, Thompson PD, Ackerman MJ, et al. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 2007;115:1643–55. [5] Maron BJ. Sudden death in young athletes. N Engl J Med 2003;349:1064–75. [6] Maron BJ, Shirani J, Poliac LC, et al. Sudden death in young competitive athletes. Clinical, demographic, and pathological profiles. JAMA 1996;276:199–204. [7] Van Camp SP, Bloor CM, Mueller FO, et al. Nontraumatic sports death in high school and college athletes. Med Sci Sports Exerc 1995;27:641–7. [8] Maron BJ, Roberts WC, McAllister HA, et al. Sudden death in young athletes. Circulation 1980;62:218–29. [9] Maron BJ, Doerer JJ, Haas TS, et al. Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980–2006. Circulation 2009;119:1085–92. [10] Drezner JA, Asif IM, Owens DS, et al. Accuracy of ECG interpretation in competitive athletes: the impact of using standised ECG criteria. Br J Sports Med 2012;46:335–40. [11] Pelliccia A, Maron BJ, Culasso F, et al. Clinical significance of abnormal electrocardiographic patterns in trained athletes. Circulation 2000;102:278–84. [12] Maron BJ. Structural features of the athlete heart as defined by echocardiography. J Am Coll Cardiol 1986;7:190–203. [13] Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA 2002;287: 1308–20. [14] Corrado P, Basso C, Schiavon M, et al. Pre-participation screening of young competitive athletes for prevention of sudden cardiac death. J Am Coll Cardiol 2008;52:1981–9. [15] Maron BJ, Link MS, Wang PJ, et al. Clinical profile of commotio cordis: an underappreciated cause of sudden death in the young during sports and other activities. J Cardiovasc Electrophysiol 1999;10:114–20. [16] Baggish AL, Hutter AM Jr, Wang F, et al. Cardiovascular screening in college athletes with and without electrocardiography: a cross-sectional study. Ann Intern Med 2010;152: 269–75. [17] Drezner J, Corrado D. Is there evidence for recommending electrocardiogram as part of the pre-participation examination? Clin J Sport Med 2011;21(1):18–24. [18] Uberoi A, Stein R, Perez MV, et al. Interpretation of the electrocardiogram of young athletes. Circulation 2011;124:746–57. [19] Huston TP, Puffer JC, Rodney WM. The athletic heart syndrome. N Engl J Med 1985;313: 24–32. [20] Fagard RH. Athlete’s heart: a meta-analysis of the echocardiographic experience. Int J Sports Med 1996;17(Suppl 3):S140–4.
ADVANCES IN PEDIATRICS Sudden Cardiac Death in Young Athletes Mohammed Mortazavi, MDa,b,* a
Department of Pediatrics, UC Davis Medical Center, 2521 Stockton Boulevard, Sacramento, CA 95817, USA; bPediatric Sports Medicine, UC Davis Medical Center, 2805 J Street, Suite 300, Sacramento, CA 95817, USA
Keywords
Sudden cardiac death Hypertrophic cardiomyopathy Automated external defibrillator Sports medicine ECG Incidence Prevention
Key points
Incidence of sudden cardiac death (SCD) is now recognized to be several times higher than once believed based on recent epidemiologic data such as the 2012 study of National Collegiate Athletic Association athletes across the country, which suggests an incidence of 1 per 44,000 athlete deaths per year.
There are multiple causes of SCD in young athletes, with most attributed to hypertrophic cardiomyopathy.
Improving ECG and echocardiography (echo) technology, along with the advent of the cardiac MRI and genetic studies, provide physicians with multiple screening and diagnostic options to identify lethal cardiac disease.
Today, multiple treatment options exist for potentially lethal structural and arrhythmogenic cardiac disorders. With the medical therapy, surgical therapy, and genetic testing available, there can be many life years saved by identifying even one previously unidentified young athlete.
For the purposes of the general pediatrician, it is critical to identify at-risk patients in the office who may require an ECG or further work up. Identification of these patients is emphasized at the preparticipation examination, but should not be excluded to athletes participating in organized sports who require clearance.
INTRODUCTION The death of a young healthy athlete has always been an unimaginable shock to the communities that endure them. These young athletes are often considered the models of health and the pillars of our society. Thus, it is difficult *Department of Pediatrics, UC Davis Medical Center, Sacramento, CA. E-mail address: [email protected] 0065-3101/13/$ – see front matter http://dx.doi.org/10.1016/j.yapd.2013.04.015
Ó 2013 Elsevier Inc. All rights reserved.
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to accept how suddenly and tragically they can fall victim to underlying deadly heart conditions. With the increase in the recognition of these tragedies, many questions have arisen regarding the best prevention strategies of sudden cardiac death (SCD) in our young population. SCD in young athletes has drawn significant attention over the last three decades, in particular with the deaths of several high-profile athletes due to various underlying cardiac conditions. Research of SCD in the young athlete has blossomed recently. As a result, many questions regarding the approach to primary and secondary prevention of SCD have manifested. As recently as 30 years ago, SCD in young athletes under the age of 35 was thought to be an extremely rare phenomenon, one that was compared with the chance of being struck by lightning. However, with improving reporting methods, screening technology, and autopsy identification of such conditions, the recent literature suggests otherwise [1–3]. There are multiple causes of SCD in young athletes with the most attributed to hypertrophic cardiomyopathy (HCM) [1,4–9]. Other common causes of SCD include anomalous coronary arteries, arrhythmogenic right ventricular dysplasia (ARVD), commotio cordis, and channelopathies [4,9]. Although myocardial infarction is the number one cause of SCD across all ages, it is a relatively rare cause in the young athlete under the age of 35, accounting for less than 3% [2,4,9]. Improving ECG and echocardiography (echo) technology, along with the advent of the cardiac MRI and genetic studies, provide physicians with multiple screening options to identify lethal cardiac disease. Today, multiple treatment options also exist for potentially lethal structural and arrhythmogenic cardiac disorders. With the medical therapy, surgical therapy, and genetic testing available today there can be many life years saved by identifying even one previously unidentified young athlete. Recent studies in Italy and the United States suggest a higher incidence of silent, potentially lethal cardiac conditions than was previously believed [1–3,10]. As a result, demand for local ECG screening campaigns and even national screening programs has grown recently. As more screening programs continue to manifest, research continues to follow the efficacy and costeffectiveness of ECG screening. For the purposes of the general pediatrician, it is critical to identify at-risk patients in the office who may require an ECG or even further work up. Identification of these patients is emphasized at the preparticipation examination, but it should not be excluded to athletes participating in organized sports who require clearance. To identify anyone at risk for SCD, questions regarding types of activity and any symptoms during activity should be asked of all pediatric patients during regular physicals. Ultimately, identification of a single, silent diagnosis that can be treated is the reason we screen thousands. EPIDEMIOLOGY AND INCIDENCE Prevention of SCD first begins with understanding the real incidence of this phenomena, which has been quite a quandary when comparing epidemiologic
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data [1,2,4,9]. Although reporting of this phenomenon in the United States has improved with increasing media and Internet coverage, there is still a significant margin for underestimation when the general US population is considered. In contrast to our Italian counterparts, the United States does not have systemic mandatory reporting registry for SCD events. In Veneto Italy, Corrado and colleagues [2,3] have been following the trends of SCD in athletes under the age of 35 since the 1970s with an established mandatory reporting system. With the advantage of a socialized health care system that serves 95% of the population requiring mandatory reporting of all SCDs, the Italian incidence data has received much recognition [2,3]. The contrast between the Italian data and US incidence data was the source for much controversy and, ultimately, one of the key reasons for dismissing considerations of ECG screening programs in the United States through much of the 1980s and 1990s. Most SCD incidence data in the United States were produced by Maron and colleagues [9]. They reported incidence rates of SCD from 1980 to 2006 in all US athletes ages 12 to 39 in 38 different sports. They analyzed 1866 sudden deaths using media reporting registries. Their initial reports of SCD in the 1980s were exceedingly rare at less that 1 per 5000,000 deaths per athlete per year. However, this data showed a rise of about 6% per year to approximately 1 per 160,000 athlete deaths per year from 2000 to 2006 [9]. The question remained, was this a true dramatic increase in occurrence of this phenomena? Or was this a result of improved reporting with the advent of the Internet and improved media surveying. During this same period, the Italians were reporting the incidence of SCD in all persons 12 to 35 in Italy in a prospective observational study [3]. They followed trends of SCD using a mandatory socialized medicine registry along with media surveying data. This data showed several interesting trends: 1. Incidence of SCD was found to be 1 per 28,000 athlete deaths per year in 1980 before the advent of a national screening program using ECGs in Veneto, Italy. 2. Most of these deaths were due to HCM, ARVD, and anomalous coronaries. 3. This incidence was 1 per 100,000 deaths per year in nonathletes at that time, suggesting that athletic activity increases the risk for SCD by about threefold. 4. This incidence of SCD and, in particular, HCM was greatly reduced over time with the advent of ECG screening in 1980.
The discrepancy in incidence between the Italian and US data raises several questions. In particular, is there a significant lower incidence in the United States? Or is the US population not as well defined and thus SCD is underreported. One explanation has been that the primarily white Italian population cannot compared with the diverse US population, which includes many African American athletes. However, studies have shown that the incidence of SCD due to HCM is two to three times as high in African Americans when compared with whites [4–6,9]. HCM is also the leading cause of death in all young athletes in the United States [4–6,9]. So the question remained, if a study was done in the United States that looked at a defined population
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with a mandatory registry data, what would the results be? A more recent study done at the University of Washington by Harmon and colleagues [1] looking at incidence of SCD in the National Collegiate Athletic Association (NCAA) among all sports and across all divisions has provided insight on this question. Results showed that there was an overall incidence of 1 per 44,000 deaths per year in NCAA athletes between 2004 to 2008. This was a substantial difference with a threefold to sixfold higher incidence from previous large US studies. When this incidence is applied to the young athlete population in the United States, about 150 to 225 deaths per year can be approximated. Subgroup analysis showed that incidence was as high as 1 per 7,000 deaths per year in male African American athletes and as high as 1 per 3000 deaths per year in male African American division I basketball players [1]. Although the absolute number of deaths studied is still limited, ongoing data collection since 2008 in this well-defined NCAA population will provide much more insight on the most accurate incidence of this phenomenon in young American athletes [1]. The data from this study has certainly highlighted the potential benefit of ECG screening in these higher risk groups as primary prevention of SCD [1]. ECG screening programs for NCAA athletes are currently being investigated in a multi-institution study. CAUSES Sudden cardiac death in young athletes has multiple causes. By far the most common cause of death is HCM, which accounts for 33% to 50% of cases of SCD [4,9]. The second most common cause of SCD in the United States is coronary anomalies of heart, accounting for 17%. This is followed by myocarditis, accounting for 6%, and several other causes such as ARVD, aortic stenosis, dilated cardiomyopathy (DCM), long QT syndrome, and other channelopathies, each accounting for 2% to 5% of cases of SCD [4,9]. Congenital heart diseases, which have a rising incidence of surviving into adolescents and adulthood also only accounted for less than 3% of causes of SCD [4–6,9]. HCM deserves special attention given its drastically higher prevalence and often silent presentation before SCD. HCM is a heterogeneous autosomal dominant genetic condition with more than 12 known genotypes and various phenotypes [4,11,12]. It results in abnormal structure and architecture of the left ventricle. HCM can lead to lethal left ventricular outlet obstruction or arrhythmia, in particular with activity. Abnormal architecture of thickened disorganized myocytes can lead to areas that undergo chronic infarction and subsequent fibrosis. These areas then become ectopic foci for deadly arrhythmias such as ventricular fibrillation. There are multiple subtypes of HCM described based on area of hypertrophy including septal, basal, apical, and concentric [4,9,12–14]. It is estimated that the prevalence of HCM is 1 per 500 in the general population and that it is more common in males and African Americans [9,12,13]. Phenotypically it is usually a silent disease without any symptoms. However, it can become suddenly lethal in certain cases, with exercise as a known trigger. When there is suspicion on history or physical, the
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diagnosis is then confirmed by ECG, echo, and specialized cardiac imaging if necessary. Traumatic causes are typically not considered when discussing common causes of silent heart diseases causing SCD. Commotio cordis is a traumatic cause for SCD that deserves attention. Several studies have quoted up to 20% of all SCD in young athletes are due to this phenomenon [15]. Commotio cordis, meaning ‘‘agitation of the heart,’’ occurs after a timely blunt force to the chest, during the T wave ascent, which causes the heart to go into lethal ventricular fibrillation [15]. Although commotio cordis can occur at any age, the mean age is 13 with a propensity for younger athletes with less developed chest walls. Studies have found modest forces such as a baseball at 40 miles per hour from 40 feet away creating enough force to set a child’s heart into commotio cordis when hit in the precordial region during the ominous 40 m T wave ascent [15]. The sensitive zone of the precordium for induction of rhythm disturbances lies between the second and fourth rib to the left of the sternum. Commotio cordis is 90% lethal unless treated with an automated external defibrillator (AED) to defibrillate out of lethal rhythms back into sinus rhythm. AEDs can increase survival rates to 35% to 50% if administered in time, with some studies quoting survival rates of 90% to 100% when AED is administered within first minute [15]. RISK FACTORS Epidemiologic studies do show some general trends of risk factors for SCD among sport, sex, and race [1,4,9]. The highest risk sports for SCD are basketball, track, cross country, football, soccer, and swimming in descending order [9]. Lower intensity aerobic sports such as Bethesda class IA and IB sports are lowest risk for SCD, thus patients with many known potentially lethal heart diseases are restricted to these sports. Males have been shown to have an overall higher incidence of SCD than females and, in particular, a higher incidence of HCM. Traditionally, males were believed to have an 8 to 12 times higher incidence of SCD than females. However, recent studies that involve higher profile elite female athletes have suggested that males only have a 2 to 3 times higher risk for SCD [1]. In particular, SCD in female swimmers was noted to be of higher incidence than males [1]. This was postulated as perhaps a result of the higher incidence of long QT in females triggered by the dive reflex in swimmers [1,4,9]. ARVD has also been noted as more common in white athletes [2,3,9]. Based on studies in the United States, ARVD was found to be a relatively rare cause of SCD when compared with HCM, and almost exclusive to whites [9]. In current Italian studies, ARVD is the most common cause of SCD in their predominately white population [2,3]. This is in part because deaths due to HCM have been greatly reduced by their ECG screening program. Overall, the incidence of SCD in African American athletes has been noted to be about two to three times that of white athletes [1,9]. There is a considerable higher incidence of HCM in African Americans, which is likely the reason for their overall higher incidence of SCD [9].
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DIAGNOSIS AND PREVENTION Diagnosis of cardiac conditions that predispose one to SCD is often very challenging. However, with a good history and physical (H&P) one can determine those in need of further testing or workup. Although these are relatively rare diseases, they can have catastrophic consequences if undiagnosed. In general, screening is best when it is most sensitive to avoid missing any diagnoses. Trying to increase sensitivity can decrease the specificity of screening, resulting in the need to rule out more initial false positives with further testing. Further testing usually involves an echo, but may require stress testing, more advanced imaging, or genetic testing. The initial H&P will be the most critical place for general practitioners to identify any red flags that indicate need for further testing. In 2007, the American Heart Association (AHA) released their most recent statement on use of a 12-point H&P with the most critical questions for prevention of SCD (Table 1) [4]. Any positive findings on H&P should warrant an ECG and possible further workup depending on ECG results. Critical questions in the medical history include any personal history of cardiac symptoms (eg, chest pain, presyncope, syncope, excessive dyspnea on exertion) during exercise. If any of these symptoms are noted, it is critical to ask follow-up questions regarding quality, severity, and timing of symptoms. In particular, the specific timing of symptoms with respect to exercise is critical to discern. If they are reported during exercise, it is important to determine if symptoms were during exercise versus before or after exercise when one would be more likely to have normal physiologic symptoms. Any history of true syncopal episodes during exercise should be discerned and referred to a cardiologist. Additional history of a previously recognized murmur or hypertension should also trigger further questioning and an ECG to rule out the possibility of underlying heart disease. Family history of SCD or disability from heart disease in a close relative under the age of 50 should also initiate an ECG. Any relative with a known, potentially lethal genetic cardiac disorder such as HCM, DCM, long QT, or Marfan disease should also trigger further workup with an ECG. Physical examination findings of a pathologic heart murmur, decreased femoral pulses, stigmata of Marfan syndrome, hypertension, or asymmetric blood pressures should also trigger further workup with ECG and cardiology referral. ECG In 2007, the AHA stance on the use of systematic ECG screening in the prevention of SCD was that this endeavor is currently too costly and not feasible as a national program [4]. They also noted potential medical legal and ethical concerns with disqualification and clearance of athletes as major barriers to having such a program [4]. Despite the Italian experience and International Olympic Committee’s stance, which recommends an H&P and ECG for every athlete, the AHA comments that the international community cannot be generalized to the US population. In the United States, there are over 10 million athletes and no infrastructure to support screening initiatives such as those that have
History and examination
Findings
Actions
Personal History
Chest pain or discomfort, presyncope during activity Syncope during activity Excessive and unexplained dyspnea or fatigue during
ECG ECG, cardiology referral ECG, rule out exercise induced asthma (pulmonary function test, exercise challenge) ECG ECG, repeat blood pressure
History of heart murmur High blood pressure Family History
Physical Examination
Any relatives who died of SCD before age 50 Close relative under age 50 with disability from heart disease Specific knowledge of certain cardiac conditions in family members: hypertrophic or DCM, long QT syndrome, Marfan syndrome, or clinically important arrhythmias Heart murmur Diminished or asymmetric femoral pulses Physical stigmata of Marfan syndrome Asymmetric of elevated (>140/90 mm Hg) blood pressure
ECG, cardiology referral ECG ECG, cardiology referral
ECG, cardiology referral pathologic murmurs ECG, cardiology referral ECG, cardiology referral ECG, cardiology referral
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Table 1 12-Point recommended participation H&P by the American Heart Association for prevention and screening of SCD in young athletes
for concerning for further imaging for further imaging for further imaging
Data from Maron BJ, Thompson PD, Ackerman MJ, et al. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 2007;115:1643–455.
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grown successful in Italy and Europe [4]. Despite this, many leagues, community programs, and volunteer organizations in the United States have began to offer screening ECGs to athletes. Several studies of ECG screening in college athletes have suggested it to be a feasible and cost-effective life-saving screening tool [1,16]. The original model for ECG screening in Italy has been shown to reduce SCD by 89% over the last 30 years [2,3]. Their initiative was spearheaded by primary care sports medicine physicians who are the work force for reading all screening ECGs. They work in conjunction with cardiologists to evaluate all athletes deemed high risk by an abnormal ECG screen. Starting with very sensitive criteria in the 1980s, they have developed more specific criteria over time and have significantly reduced the false positive rate to less than 20% [2,3]. The University of Washington has been screening NCAA athletes with only a reported 10% to 12% false positive rate, using sports medicine physicians to lead the initiative to screen all athletes with ECGs [17]. A 2010 study at Harvard using echo confirmation found three athletes with potentially lethal heart disease out of 500 screened, two of which (HCM, myocarditis) required the ECG to make the diagnosis [16]. This study reported a false positive rate of 17% with screening ECGs [16]. A recent study done in Colorado that performed H&P along with screening ECG for 1000 high school athletes ages 13 to 18 found two potentially lethal diagnoses (long QT and WolffParkinson-White [WPW] syndrome) based solely on the ECG screens. ECGs were read by a pediatric sports medicine primary care physician (PCP) before a pediatric cardiologist and a false positive rate of about 11% was noted from the initial PCP reads. Many ECG screening programs are now using PCPs or primary care sports physicians in primary prevention of SCD. These programs all follow different models but, in general, PCPs are used for first-line screening of ECGs using very sensitive guidelines [2,3,17,18] Any positive findings are sent to cardiologists for review and determination if a cardiology consult is warranted based on the ECG findings. This approach may lead to a large number of false positives that require cardiology read or consults with further testing required. However, the literature shows the false positive rates have dramatically decreased over the last 20 years with the use of more specific ECG interpretation guidelines [18]. With continuing research, the first-line screening criteria initially established by Corrado and colleagues in Italy over three decades ago has grown more specific while maintaining an expected high sensitivity [2,3,11,18]. ECG INTERPRETATION The ECG criteria can be systematically reviewed by any PCP who is comfortable reading basic ECGs. Beginning with rate, rhythm, and axis, the PCP should evaluate for tachycardia, bradycardia, arrhythmia, and axis deviations. Heart rate (HR) in a young athlete is expected to be 60 to 100, but can be as low as 30 in the conditioned athlete [11,19,20]. True bradycardia with HR less than 30 should be assessed for heart block or sick sinus syndrome. Tachycardia is less common in athletes and thus the age of athlete must be considered as
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well as any recent activity or cause for anxiety during pulse examination. If true tachycardia is repeatedly noted, superventricular tachycardia (SVT) should be considered. With SVT, HR is typically greater than 220 and there is no beat-to-beat variability. Arrhythmias to screen for include atrial fibrillation, atrial flutter, and any other ventricular arrhythmias. Greater than two premature ventricular contractions (PVCs) per ECG strip should also warrant further investigation with repeat ECG or cardiology consult. True axis deviation may suggest several pathologic findings such as right ventricular hypertrophy (RVH) or HCM. Using the more refined criteria, evaluation for any right axis deviation greater than 115 and left axis deviation greater than 30 would be cause for concern and cardiologist consult [18]. Assessment of axis deviation in the pediatric athlete must also consider the age of the athlete. Rightward axis deviation, which is normal at birth, transitions to leftward axis in adolescence and adulthood depending on age. Thus, some younger athletes may still have normal transitioning right axis deviation. Other factors that can cause pathologic axis deviation include chronic pulmonary disease or systemic hypertension, in which case further cardiology workup is warranted [18]. Next, a review of ECG for any abnormal atrial abnormalities should be done. This involves an evaluation of the P waves, which represent atrial contraction. Any P wave greater than 2.5 mV in amplitude in any lead is concerning for right atrial enlargement. Left atrial enlargement manifests with prolonged total duration of the P wave greater than 120 ms, or a negative deflection of the P wave in V1, V2 that is both greater than 1 mV in amplitude and greater than 40 ms in duration. Atrial abnormalities are often found to be nonpathologic, but can be related to RVH, HCM, and increased pulmonary resistance, and should warrant a cardiology consult. After reviewing the morphology of the P wave, the PR interval should be calculated to rule out any findings of heart block. First-degree heart block or a PR interval of 200 to 300 ms is considered to be a normal physiologic manifestation of increased vagal tone seen in athlete’s heart (AH) [11,12,19]. PR intervals greater than 300, progression of the PR interval, dropped P waves, or P-QRS dissociation are concerning for second and third degree heart block that should be further evaluated. A thorough evaluation of the QRS complex should be done starting with the depth and width of Q waves. Abnormally wide or deep Q waves should rise concern and trigger further workup. Any Q waves deeper than 3 mV or longer than 40 ms in any leads other than leads III, AVR, AVL, and V1 should initiate a cardiology consult. Evaluation of QRS complex starts by ruling out any up-slanting QRS complex with short PR interval, usually less than 120 ms, that would be consistent with delta waves seen in WPW syndrome. Evaluation of the QRS complex should also involve assessment for any bundle branch blocks, or interventricular conduction delays (IVCDs), defined by a QRS interval greater than 120 ms. Right and left bundle branch blocks can be identified based on their specific morphology in V1 (RSR9 , QS) and increased QRS interval greater than 120 ms. Most IVCDs in asymptomatic
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patients will lead to normal imaging and workups. However, associations with HCM, atrial septal defects, and Chagas disease in endemic countries exist [18]. Thus, IVCD should be taken seriously and cardiology consulted for possible further workup. Most computer interpretations will be more accurate than standard measurements for QRS duration and should be reviewed carefully along with visual inspection for any specific bundle branch block morphologies. The R and S wave amplitudes should be measured to determine if there are any abnormally large amplitude concerning for RVH or left ventricular hypertrophy (LVH). In general, large R wave amplitudes in anterior leads such as V1 can be a sign of RVH. Specific recommendations include assessing for any R wave greater than 7 mm in V1, R/S ratio greater than 1, or the sum of the R wave in V1 and S in V5 or V6 that is greater than 10.5 mV [18]. These findings may warrant further workup for RVH, especially in athletes older than 30 years of age [18]. Any of the above findings for RVH plus right atrial enlargement, right axis deviation greater than 115, or T wave inversion in V2 or V3 are specifically concerning for pathologic RVH in the young athlete under the age of 30 and warrant further workup [18]. LVH typically presents with prominent R waves now in the lateral leads V4 to V6 or deep S waves in the anterior leads. There are several different methods of assessing for LVH including the Sokolow-Lyon Index (SLI) and Cornell voltage criteria. No one method is perfectly sensitive or specific, but use of combined criteria can improve sensitivity and specificity. Using the SLI, the sum of S in V1 and R in V5 or V6 greater than 35 mV is considered isolated LVH. This correlates with echo measurements of greater than 10 to 12 mm of concentric left ventricular myocardial wall thickness [11]. Isolated LVH is a very common finding in conditioned athletes secondary to physiologic hypertrophy and remodeling of the heart muscle in response to exercise. When findings of LVH are isolated without any other associated abnormalities, such as Q wave abnormalities, lateral lead T wave inversions, or ST changes, no further workup is necessary [18]. There have been several postulations that perhaps LVH can be a precursor to HCM; however, there is no evidence in the literature to suggest this. There is no study done to date that has followed a group of young adolescents with LVH to determine if any develop pathologic heart disease such as HCM. ST CHANGES OR T WAVES ST segment changes may be associated with HCM and ARVD due to areas of infarction secondary to abnormal myocyte and vessel architecture. Any ST segment depression greater than 0.5 mV below the isoelectric line in the lateral leads, AVL, or lead I are concerning and should warrant further workup. ST segment depression greater than 1 mV in any lead should also warrant further workup. ST changes secondary to coronary artery disease and myocardial infarction are rare in the young athlete. However, other silent lethal cardiac diseases such as HCM and ARVD can present with ST depression without
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associated hypertrophy patterns on ECG [3,5,9,18]. ST segment elevation in lateral leads V3 to V6 that is less than 0.5 mV is commonly seen due to early repolarization in conditioned athletes and is a very common finding in AH [11,12]. Early repolarization may or may not be associated with LVH also commonly seen conditioned athletes. Recent epidemiologic studies have shown prevalence of greater than 50% in conditioned adult athletes [11,12,19]. Physiologic early repolarization can be confused with the abnormal J wave seen Brugada type 1 pattern, which resembles ST elevation from the isoelectric point. However, Brugada pattern is seen in V1 to V3, and the characteristic J wave usually has ST elevation significantly greater than 0.5 mV. Any ST segment elevation in V1 to V3 should be evaluated closely for Brugada syndrome and warrant cardiac consultation. Postexcitation potentials or epsilon waves are also seen in leads V1 to V3 with a post-QRS hump pattern seen before the T wave. Epsilon waves are usually associated with a T wave inversion. This pattern has been associated with ARVD and other cardiac pathologic conditions and deserves further workup [18]. T WAVE INVERSIONS OR QT CHANGES T wave inversion in certain leads can be concerning ECG findings. T wave inversions have been noted in 2% to 4% of the adult athlete population without any cardiac disease [18]. It is important to recognize that T wave inversions in anterior leads V1, AVR, and III can be normal. In females and children, T wave inversion in V1 to V3 is typically normal. T wave inversions in athletes under 18 were noted in the anterior leads in up to 20% of athletes [18]. Studies looking at T wave inversions in African Americans have noted an incidence of 14% and normal T wave inversion patterns in V2 to V4 [18]. However, if significant T wave inversions greater than 1 mV are noted in any of the lateral or inferior leads further workup is warranted. The European Consensus Statement has suggested any T wave inversions greater than 2 mV in two or more contiguous leads should be considered as a very significant abnormality requiring definite workup [18]. QT INTERVALS QT interval changes should be closely measured and reviewed for any prolonged or short QT syndromes. Criteria suggest QTc measurements in lead 2 or V5 using standard measurement of QT interval divided by square root of preceding RR interval. Any QTc measure less than 340 ms is considered short QT and requires referral. More commonly, long QT syndrome is seen defined by QTc greater than 470 in males and greater than 480 in females [18]. A QTc of 440 to 470 is considered borderline and should be followed with a repeat ECG or a stress ECG. Long QT syndrome is well defined with several different genotypes isolated and strongly associated with SCD risk. Long QT type 1 is the most common genotype, with exercise as the main known trigger for SCD. Genetic testing for the QT genotype can help determine appropriate therapy and prevention strategies as well as confirm
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diagnosis. These include treatments with beta blockers, activity restriction, and implantable cardioverter-defibrillators (ICDs). Family genetic testing can also help determine if other high-risk family members have the syndrome and may require treatment. ECG CRITERIA FOR AH AH is a phenomenon that must be well understood in the interpretation of screening ECGs and prevention of SCD. The recognition of this phenomenon is not to identify uniquely conditioned hearts, but instead to prevent mistaking them for abnormal hearts. ECG criteria for AH include any one or combination of the following: 1. 2. 3. 4. 5.
Bradycardia First-degree atrioventricular block Incomplete right bundle branch block LVH Early repolarization.
These findings in a young athlete should be expected and considered as normal. Identification of ECG findings of AH is critical to recognize to prevent many false positives. ECG criteria for AH is seen in up to 80% of elite adult athletes and 60% of pediatric athletes [4,12,19]. Comfort with routine recognition of these findings is important for the PCP to prevent a large influx of unnecessary referrals and workups. FURTHER WORKUP Patients with concerning findings on H&P or ECG often will need to be referred for further cardiac workup. In general, any of the concerning ECG findings on (Table 2) should be reviewed with a cardiologist to determined whether a referral is needed [18]. Findings consistent with AH (Table 3) are normal and require no further workup if indeed ECG is limited to these isolated normal physiologic training changes. Despite ECG findings, any concerning symptoms such as true syncope, palpitations, or chest pain during exercise should be referred. The additional workup by a cardiologist will depend on the diagnosis of suspicion. In general, this will involve an ECG, echo, and other possible workup. Stress ECGs may be required to make certain diagnoses such as catecholaminergic polymorphic ventricular tachycardia (CPVT), which is a lethal arrhythmia that is solely exercise induced. Cardiac MRI provides very detailed imaging of cardiac anatomy, which can be very helpful in multiple diagnoses including HCM, ARVD, and anomalous coronaries. Cardiac MRI can be performed dynamically to assess function, or with gadolinium to highlight abnormal cardiac tissue and fibrosis. Genetic studies available for disorders such as HCM and long QT are very helpful in characterizing the disease for optimum treatment when phenotypes are gene positive. Family genetic testing is important in all gene positive patients to help identify others that may have been affected by the disease.
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Table 2 Abnormal ECG findings Assessment
Abnormality
ECG criteria
Rate
P waves
Sick sinus syndrome SVT PVCs Ventricular arrhythmias Atrial fibrillation Atrial flutter Left axis deviation Right axis deviation Left atrial enlargement
PR intervals
Right atrial enlargement Second-degree heart block
Q waves
Third-degree heart block Abnormal Q waves
QRS
Delta wave
ST changes
Left bundle branch block Right bundle branch block IVCD RVH ST segment depression
HR <30 HR >220, no beat-to-beat variability 2 or more per ECG — — — More leftward than 30 More rightward than 115 P wave >120 ms OR P wave with negative deflection in V1, V2 with >1 mV, >40 ms P wave >2.5 mm in any lead PR >300 ms Prolonged PR intervals, Dropped P waves P-QRS wave dissociation (>3 mV) OR (>40 ms) in any lead except III, aVR, aVL, or V1 Up-slanting QRS (delta waves) and PR <120 ms QRS >120 ms in V1 with QS wave pattern QRS >120 ms in V1 with RSR9 pattern QRS duration >120 ms in any lead R wave >7 mm in V1 or R/S ratio >1 >0.5 mm below isoelectric line before T wave in leads V4, V5, V6, I, aVL or >1 mV in any lead Epsilon waves with T wave inversion V1 to V3 J-wave pattern in any of V1, V2, or V3 >1 mV in any lead other than V1, III, aVR (except V2, V3 in females) >470 ms males, >480 ms females <340 ms
Rhythm
Axis
Postexcitation potentials
T waves QT abnormalities
Brugada type 1 pattern T wave inversion Long QT Short QT
MEDICAL PREVENTION Diagnosis of potentially lethal cardiac disease is critical to initiating medical management to prevent a sudden cardiac event or death. Depending on the cause, multitude medical options exist that are usually initiated and managed by a cardiologist. With the diagnosis of HCM, medications such as beta blockers may be started. Activity restriction to class IA sports per the Bethesda classification is recommended. ICDs are placed in some higher risk patients or patients with a history of near death events. A recent high-profile professional soccer player in Europe with the diagnosis of HCM did not comply with activity restriction recommendations and returned to soccer after treatment with beta blockers and an ICD. He had a subsequent event that would have likely resulted in death; however, while lying pulseless, his ICD shocked and revived him.
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Table 3 Normal ECG findings of AH Finding
ECG criteria
Sinus bradycardia First-degree heart block Incomplete RBBB Early repolarization Isolated LVH
HR 30–60 beats per minute PR 200–300 ms V1 RSR9 morphology with QRS 100–120 ms ST elevation <0.5 mV in V3–6 S in V1 and R in V5 or V6 35 mV
Depending on area and severity of cardiac hypertrophy, a surgical myomectomy can be performed to prevent outlet obstructions. When known ectopic foci of arrhythmias exist, such as in WPW or certain cases of HCM or ARVD, ablation therapy can be used to ablate these foci. Channelopathies, such as Brugada syndrome, CPVT, and long QT syndrome, can be treated with beta blockage and anti-arrhythmic agents depending on specific type diagnosed with genetic testing. Primary prevention of SCD begins with a thorough, well-informed H&P following the AHA 12-point questionnaire, followed by ECG screening for any high-risk athletes. Primary prevention also involves awareness and education of both the athletic and medical communities. The cost and effort spent on primary prevention to save a single life must be understood by all parties involved to have a successful screening program. Secondary prevention involves being prepared to prevent a death when an event occurs. Too often, silent lethal cardiac conditions manifest for the first time as lethal arrhythmias or outlet obstructions leading to asystole. Cardiopulmonary resuscitation is the most helpful and applicable skill that can help directly save lives in these situations. The availability of AED devices can be critical in situations with shockable rhythms. Most deaths caused by HCM and commotio cordis are due to lethal ventricular fibrillation that can be shocked back to sinus rhythm by an AED. Most modern AEDs are very easy to use with simple three-step directions. Education about the function, use, and potential life-saving capabilities of AEDs are critical for community providers and officials. Funding and availability for AEDs has greatly increased in recent years and, today, many facilities such as schools and gyms will have an AED available. Healthcare professionals covering any sporting event should check with officials on the location of the AED and be prepared for its use, if necessary. References [1] Harmon KG, Asif IM, Klossner D, et al. Incidence of sudden cardiac death in National Collegiate Athletic Association athletes. Circulation 2011;123:1594–600. [2] Corrado D, Pelliccia A, Heidbuchel H, et al. Recommendations for interpretation of 12-lead electrocardiogram in the athlete. Eur Heart J 2010;31:243–59. [3] Corrado D, Michieli P, Basso C, et al. How to screen athletes for cardiovascular diseases. Cardiol Clin 2007;25:391–7, v–vi.
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