Review Article Open Access
Part 2 - Sudden Cardiac Death in Athletes Focused Cause-and-Effect Screening
Timothy E. Paterick1*, Naila Choudhary2, Krishnaswamy Chandrasekaran3, A. Jamil Tajik5, and Jim Seward4
1Professor of Medicine, Director of Noninvasive Imaging, University of Florida College of Medicine, Jacksonville, FL, USA
2Cardiology, Fellow , University of Florida , College of Medicine, Jacksonville, FL, USA
3Professor of Medicine, Mayo College of Medicine, Rochester, MN, USA
4Professor of Adult and Pediatric Cardiology, Emeritus Nasseff Professor of Cardiology, Mayo Clinic, Rochester MN, USA
5Professor of Cardiology, Pediatrics and Adult Congenital Heart Disease, Aurora St. Luke’s Medical Center, Milwaukee WI, USA
*Corresponding author: Timothy E. Paterick, Professor of Medicine, Director of Noninvasive Imaging, University of Florida College of Medicine, Jacksonville FL, USA; E-mail: @
Received: June 25, 2015; Accepted: November 09, 2015; Published: December 31, 2015
Citation: Paterick TE, Choudhary N, Chandrasekaran K, Tajik AJ, Seward J (2015) Part 2 - Sudden Cardiac Death in Athletes Focused Cause-and-Effect Screening. J Exerc Sports Orthop 2(4): 1-13.
Abstract
Sudden death in an athlete is a tragic event. There is a strong social imperative to implement effective means of predicting and preventing sudden death in athletes. However, the design and implementation of a solution seems unobtainable [2]. Part Two discusses how novel attributes of systems biology and digital technology are capable of delivering high quality, low cost athletic screening. The merit of a transformative idea does not necessarily predict its adoption. The greatest barrier to change lies in the acquiescence to familiar practices even in light of new ideas and technology. The current thought in athletic screening is more centered on specific disease associations (rule-in principle), [3-5] and much less about the sensitivity of pathophysiologic causality (ruleout principle) [5-8].

A solution will languish until the expert community takes direct action to embrace 21st century systems based medicine, causality, and digital technology [7,9,10]. The first step is to break the code of silence by open public discourse (publish and speak about the transformative attributes of systems based medicine).The second step is to make everyone accountable (causal prediction and prevention must be 100%). The third and final step is to focus on how to define the components of systems based medicine, determine how these components interact with one another, and delineate the dynamics of these components in determining pre-emergent disease states [10].
Introduction: Why and How
Why? [11] Although sudden cardiac death in athletes is rare, most of these individuals are young, healthy and otherwise would have long productive lives. Their loss is shocking and can be prevented.

How? Every essential screening test must detect normality, and on the other hand alert the presence and intensity of a potential life threatening abnormality with a very low rate of false positives. An essential screening exam should emphasize prognostication and not the permutations of disease detection [12]. Athletes are known to have normal to hyper-normal physiology, while life-threatening diseases have distinctly abnormal physiology.

Echo/Doppler screening should be looked upon as a strategy used in a select population of healthy, asymptomatic individuals to identify pre-emergent disease. Using focused echo/Doppler screening the incidence of a cardiovascular finding in athletes has been reported to be roughly one case in every 170 athletes screened with a "false positive" finding in only 8 of 508 athletes [2, 10, 13-15]. We describe how to provide a highest quality, exceptionally low cost pathophysiologic athletic screening test, which is validated to differentiate the status of a normal state from an abnormal life-threatening pathophysiologic state.

Matching pre-emergent disease (without phenotypic expression) "associated" with sudden death through diastolic parameters is the key to differentiating normal from abnormal pathophysiology [5, 9, 16-24]. These data are focused on two principal objectives: detect an imminent life-threatening state at a time when the opportunity for prevention is optimal [25, 26], and define the magnitude of imminent risk that enlightens physician decision making and management [23, 26-28].
Rule-Out vs. Rule-in Screening
A sensitive screening approach must be distinguished from a specific screening methodology [5, 6]. The current trend in athletic screening is searching for an "abnormal" disease feature in a low risk population. This fact alone (searching for a specific rare event) is a major contributor to the controversies and shortfalls surrounding athletic screening [5, 6].

The most optimal screening test for a large, asymptomatic athletic population prioritizes testing to confirm wellness and rule out disease. An abnormality in screening would be referred for comprehensive evaluation. The rule out principle is important because the penalty for missing a disease has the potential for athletic death. This principle reduces the number of specific diseases to be considered during screening. All cardiomyopathies are grouped as having abnormal diastolic tissue Doppler examination. Conversely, ruling in a disease is more applicable when confirming a high frequency disease. Confirming wellness and ruling out disease is most applicable to large, asymptomatic athletic population [5, 6].

The testing that depicts pre-clinical disease is diastolic function [29]. Primary diastolic dysfunction occurs early in the emergence of cardiomyopathies, hypertension, valvular, and ischemic heart disease Table 4. Doppler-echocardiography is recognized as the most useful tool to routinely and economically quantify diastolic and systolic function [29-34].
Causes of Sudden Death
Sudden cardiac death is most commonly due to a quiescent pathophysiologic "trigger" that can become malignant if the “trigger” is disturbed. There are 3 principal types of triggers: cardiomyopathies, channelopathies, and structural heart disease. The nature of individual and overlapping triggers vary not only by an underlying disease state, but also by pathophysiologic state, genetic determinants, and environmental factors [33, 35]. People with cardiomyopathies commonly die an arrhythmia death[36]; people with channel opathies may experience arrhythmia death [37]; and people with structural diseases may experience cardiac dysfunction and arrhythmia deaths [38]. The causes of sudden cardiac death promote blunted micro and macro-vascular ischemia and replacement fibrosis, which cause electrical heterogeneity, and induced arrhythmias [39, 40]. The state of a "trigger" can be measured as an aggregate of multiple related features [7-9, 41]. In athletes a quiescent "trigger" can suddenly transitioninto amalignantstate due to the physiologic stress of exercise [29, 42-44].In vulnerable athletes exercise changes LV compliance, rather than LV systolic function[45]. The distinction between a normal and abnormal "trigger" lies in the aggregated pathophysiologic profile of small groups of highly related features of diastolic function [9] Table 1 and 2.
Cardiomyopathies
Normal CV function can be effectively and reproducibly measured as a small set of related echo/Doppler data [30, 46, 47] Table 1 and 2. Essential screening for cardiomyopathies is not designed to define a specific disease, but should be focused on the imminent risk of sudden death. Risk is most easily and accurately defined as a weighted expression [22, 23] of a small group [16, 17, 28, 48] of linked diastolic parameters [9, 49]. The essential focused echocardiographic approach has been validated to have a very low incidence of false positive and false negative interpretations[9, 14, 48, 50]. Outliers within a disease module can be appropriately classified [48]. In most circumstances only 2 to 4 aggregated diastolic features (e’, E/e’ ratio, DT, E/A ratio) will suffice to differentiate normal vs. abnormal pathophysiology [51].

Asymptomatic diastolic myocyte dysfunction followed by systolic myocyte dysfunction and microvascular ischemiaemerge early in the pathophysiologic continuum, while structuraland electrical remodeling (electrical heterogeneity, arrhythmogenesis, and fibrosis) and symptoms occur later [60]. The prognostic importance of asymptomatic pre-emergent pathophysiology has only recently been realized [61, 62]. Asymptomatic athletes commonly engage in activities that can accentuate pre-emergent pathophysiology that could be acutely detrimental to myocardial function. For screening purposes "cardiomyopathy" can theoretically apply to almost any disease affecting the heart in which the heart muscle is structurally abnormal. Essential screening should be focused on prognostication of risk ,and not detection, or characterization of a disease type [12, 63]. An essential examrequires the acquisition of a small number of essential data, which define the presence and intensity ofemergent cardiac dysfunction Table 1. Disease risk is always defined by more than one datum feature. Hypertrophic cardiomyopathy (HCM) is an exemplary candidate for pathophysiologic screening. HCM rarely has any premonitory symptoms [35], even under exertion [35], ECG has a high rate of false positives [64-67], ejection fraction (EF) is rarely abnormal,[32]and anatomic remodeling is variable, and typically occurs late in the pathophysiologic cascade [68]. However, associated diastolic dysfunction can be detected and measured early in the HCM cascade [68-70] and is capable of detecting pre-clinicalHCM risk [68, 69, 71]. An essential screening exam is the one designed to affirm the existence of anormal physiologic profile, and identify individuals with an abnormal risk profile, independent of morphology Table 2 [9, 21, 28, 72].The algebraic summation of a small aggregate of related data (E/A, DT, e’, E/e’)define causality [28, 41] which mirrors the status of an individual’s risk state in both a positive and negative direction during serial screening, management, and follow-up [7, 8, 73].

Cardiomyopathy-screening needs to take a focused approach to potential emergent cardiac dysfunction and risk [36, 74]. Each cardiomyopathy disease(hypertrophic [68, 75], restrictive [76, 77], dilated[78], ischemic [79, 80], hypertensive [81, 82], arrhythmogenic right ventricular [83], myocarditis [84], left ventricular non-compaction [85, 86]) each has validated pathophysiologic features that can confirm a risk state [52, 87]. Averaged features have a very low incidence of false positives and false negatives results [9, 14, 48, 50].
Hypertensive Heart Disease
The essential pathophysiologic data used to depict the risk of hypertensive heart disease [81, 82] and "pseudo-HCM" [48, 91, 92] are identical to those of general cardiomyopathies [60] Table 1&2. Screening blood pressure and increased LVwall thickness serve only as benchmarks that require physiologic classification as normal compensatory physiology versus emergent heart disease [91]. The overlapping features of normal [9, 54, 93] myocardial remodeling can mimic the features of HCM, hypertensive heart disease, and infiltrative diseases [81, 94]. These overlapping features have been referred to as the "gray zone". The overlapping features are not essential to an essential, focused examination attempting to determine risk. The goal of essential screening is to affirm normal and rule out abnormal disease related remodeling [5].
Ischemic Heart Disease
Although considerable attention is focused on young athletes, the risk of sudden death from coronary artery disease (CAD) is much greater among sports participants older than 35 years
Table 1: Mechanical Features [30, 47].
  • E = early transmitral filling velocity related to the time course of active LV relaxation, which generates a gradient from left atrium through the left ventricular inflow.
  • Lateral e’ = early diastolic annular velocity measured in the lateralregion of the mitral annulus; Most patients with lateral e’ ≥8.5 cm/s have normal myocardial relaxation [30].
  • Septal e’ = early diastolic annular velocity measured in the septal region of the mitral annulus; reflects longitudinal diastolic myocardial relaxation; Most patients with septal e’ ≥8cm/s have normal myocardial relaxation [30];
  • E/e’ ratio: E/e’ ratio is a surrogate measure of LV filling pressure [43]. Average of lateral and medial E/e’ <8 would have normal myocardial relaxation and LV filling pressure [30].
  • S’ = systolic velocity of mitral annulus
  • A = late transmitral filling velocity
  • DT = Transmitral Deceleration Time; tends to be prolonged by impaired LV relaxation and shortened by                   increased filling pressure.
  • EF= Ejection Fraction
  • GLS = Systolic Global Longitudinal Strain
  • LAVI= Left Atrial Volume Index [51]
  • Table 2: Normal Multi-feature Screening Physiology [30, 47].

    Diastolic Function

    Normal

     

    Reference

    Mitral inflow E (cm/s)

    60±12

     

    [47]

     

     

     

     

    Diastolic velocity MV annulus

    Normal e’ by Age group (y)

     

     

    16-20

    21-40

    41-60

    >60

     

    Septal e’ (cm/s)!

    Lateral e’ (cm/s)!

    14.9 ± 2.4

    20.6 ± 3.8

    15.5 ± 2.7

    19.8 ± 2.9

    12.2 ± 2.3

    16.1 ± 2.3

    10.4 ± 2.1

    12.9 ± 3.5

    [30]

     

     

     

     

    E/e’

    NormalE/e’

    (& Normal e’)

    Abnormal

    E/e’

    (& Abnormal e’)

     

    Septal E/e’ ratio

    Lateral E/e’ ratio

    7.05±6.0

    6.18±1.53

    8-10

    >8-9

    11-14

    10-11

    ≥15

    ≥12

    [30, 47]

    Average E/e’ ratio

    <8

    9-12

    >13

    [30]

     

     

     

     

     

     

    MV inflow E/A ratio

    if the e’ is normal

    >0.8 to <2*

     

    If e’ is abnormal these same data ranges would be abnormal (i.e. pseudonormal)

     

    [30]

     

     

    MV inflow DT

    if the e’ is normal

    >140 to <240*

     

     

     

     

    Left Atrial Morphology

    Normal

    LA overload

    [51]

     

    LA Volume Index (mL/m2)

     

    16 to 28

    22±6

     

    Mild

    29-33

    Moderate

    34-39

    Severe

    ≥40

    [52]

    Benign if e’ is Normal

    [51, 53]

    Malignant if e’ is Abnormal

     

     

     

     

    Systolic Function

    Normal

     

     

    EF %

     Artifactual EF %*

    ≥55

    50-55

    Athletes with Large LV; EF can appear mildly reduced; if diastolic function is normal the low EF is likely an artifact

     

    [54]

    Global Longitudinal Strain %

    -19.7

    (As the negative number increases the function improves)

    [55, 56]

    Tissue Doppler s’ (cm/s)

    Septal

    Lateral

     

    >7.5

    10±1.5

     

     

    [57]

    RV systolic Function (cm)

    Tricuspid Annular Displacement

    TAPSE (cm)

     

     

     

    ≥1.8

     

     

     

    [58]

     

     

     

     

    ! Data are expressed as mean ± SD. Note that a normal e' velocity in subjects aged 16 t 20 years, values overlap with those for subjects ages 21 to 40 years. This is because e' increases with age in children and adolescents. Therefore, the e' velocity is higher in a normal 20-year-old than in normal 16-year-old, which results in a lower e' value when subjects aged 16 to 20 years are considered [30].
    *EF between 50-55% [54] (LV cavity enlargement in normal athletes can be associated with a modest lowering the EF).The presence of normal diastolic function would strongly suggest normal athletic CV remodeling and not physiologic dysfunction.
    ! GLS (Global Longitudinal Strain) is a measure of sub-clinical systolic function. There is a universal pathophysiologic cascade inprimary and secondary cardiomyopathies [39, 59]
    and is greatest in the fifth decade [95-97]. The incidence of fatal CAD is reported to be 0.7 per 100,000 person - years for athletes <35 years of age, and 13.7 per 100,000 persons-years for those ≥35 years of age [98]. Ischemic risk represents the cumulative impact of a cascade of pathophysiologic events [59]. The focus on the late stage features of CAD (ECG abnormalities, angina, wall motion abnormality and infarction) needs to be redirected to the more fundamental underlying pathophysiologic factors (subclinical diastolic and systolic dysfunction) that emerge earlier in the pathophysiologic cascade [59]. The essential objective of screening asymptomatic athletes is to disclose imminent pathophysiologic risk (occurrence of an event within 1 year [99], and not the presence of long-term risk (Framingham Score 10 year risk profile [100]). Screening stress testing [67, 101-103] and CT coronary angiography [104] are considered inadequate means of assessing CAD risk in asymptomatic adults. Coronary calcium score may be helpful to determine the burden of CAD, but at this time the risk associated with a particular calcium score is unknown [105] and deemed an inappropriate marker for those at low risk [106]. In an asymptomatic population, echocardiographic physiologic dysfunction asan indicator of asymptomatic life threatening cardiac dysfunction is often underappreciated [69]. In asymptomatic adults, resting echo/Doppler diastolic function assessment Table 1&2 is reported to be an excellent independent predictor of imminent CAD risk [107-111].

    There is controversy regarding the means of quantifying imminent CAD riskin asymptomatic athletes (92). At present, recommendations for the assessment of imminent risk are limited, inconsistent, or nonexistent [101, 108, 112]. However, echo/Doppler determination of an individual’s physiologic state is a logical general predictor of imminent risk, includingthe risk of ischemic heart disease. If the physiologic risk was sufficiently abnormal further assessment ofcoronary anatomy and physiology would be clinically indicated particularly in individual’s ≥35 years old. As the population ages, the incidence of pre-clinical risk associated diastolic dysfunction increases [61, 62]. This fact supports the use of essential screening in the general population just as screening is used withother disease processes (e.g., colonoscopy [113]; mammography [114]; and often CV disease [115]).
    Channelopathies
    Channelopathies are considered unique and are variably classified asa primary electrical disease or cardiomyopathy [36, 60]. Various forms of electrical cardiomyopathy affect about 1 in 1000 people[116].Channelopathies are the assumed culprit in cases of undefined sudden death [65]. Randomized and/or blinded studies do not exist in this field. All recommendations are based on consensus opinions [117]. An important clinical finding is that 50% of these sudden death victims have preceding "warning signs": exercise /auditory triggered fainting/ seizures, family history of premature CAD (<40 years of age), or unexplained accidents, and near drowning [116].

    Proper recognition ofthesewarning signsmay significantly reduce primary electrical deaths and initiate amore comprehensive electrophysiology workup [65, 118]. Currently technical and logistical challenges preclude the use of ECG as a robust tool for universal screening in asymptomatic population [116,119]. One of the biggest challenges with ECG is the high incidence of false positive findings [66, 118]. Interestingly in recent research subclinical Doppler pathophysiologic changes were identified in nearly 20% of Long QT syndrome patients [120]. These findings prompt speculation that electrical dysfunction (abnormal cardiac repolarization and rhythm) may precipitate macroscopic structural and functional changes visible on focused echocardiograms [120, 121].
    Structural and Hemodynamic CardiacDisease
    Pulmonary Hypertension
    Pulmonary artery pressure (PAP) can be estimated in nearly 100% of patients using any one of three simple techniques [122]: (1) Systolic PAP using the Tricuspid Regurgitant Velocity (TRv) (Normal TRv≤2.8 m/s corresponding to a right atrioventricular gradient ≤31 mmHg] is considered a reasonable cutoff to define elevated PAP in healthy persons; (2) Normal Diastolic PAP using the end-diastolic Pulmonary Regurgitant Velocity(PRv) (PRv <1.1 m/s corresponding to an end-diastolic pressure of <5 mmHg] is correlated with normal pulmonary pressure.; and (3) normal mean PAP using pulmonary flow acceleration time (AcT) (AcT defined as the time interval from the onset of forward flow in the PA to peak velocity of this flow). AcT >100 ms equates a mean PAP < 20-39 mmHg and AcT <75 ms equates to a mean PAP ≥40 mmHg [123,124] Table 3.
    Coarctation of aorta
    Is a rare cause of hypertension.It should be excluded in every patient with elevated blood pressure, or in the presence of a BAV [126]. Coarctation cannot be effectively detected by random blood pressure measurements or a cursory physical exam [24], but can be detected and quantified by a simple echo/Doppler signal in the abdominal aorta [127]. In the presence of coarctation the overall aortic velocity is blunted, systolic upstroke is delayed and there is continuous forward flow consistent with a diastolic and systolic gradient and/or collateral flow. These abdominal aortic pulsed-wave Doppler signals were recorded in a normal patient (upper panel) and a patient with severe coarctation of the aorta (lower panel). The normal tracing (upper) shows a rapid systolic upstroke and return to baseline at end-systole. The early diastolic reversal of flow associated with a widely patent aortic arch. Elastic recoil of the ascending aorta causes the low velocity, late-diastolic forward flow seen after the early diastolic reversal.
    Table 3: Pulmonary Artery Pressure Screening (125).

    Measure

    Equivalent PAP

    Normal Values

    Reference

    TRv m/s

    (Systolic PAP)

    ≤2.8 m/s (>31mmHg)

    [122]

    PRv m/s

    (End Diastolic PAP)

    ≤1.1 m/s (≥5 mmHg)

    [122]

    Pulmonary AcT

    (Mean PAP)

    >100 ms (<20-39 mmHg)

    <75 ms (≥40 mmHg)

    [122-124]

    PAP: Pulmonary Artery Pressure; TRv: Tricuspid Regurgitant Velocity;
    PRv: Pulmonary Regurgitant Velocity; AcT : Acceleration Time
    In contrast, in the presence of coarctation (lower panel) overall velocity is blunted and the systolic upstroke is delayed. Although the systolic velocity is decreased, the diastolic velocity is actually greater than normal. This case shows continuous forward flow, consistent with both systolic and diastolic gradients across the coarctation.
    Anomalous Coronary Artery
    An essential component of every athletic screening examination is the visualization of the origin of the proximal coronary arteries, which can be accomplished with transthoracic echocardiography in 70 t oover 95% of young athletes [14, 66, 128-130].Other technologies (e.g., MR and CT) do not fit the essential qualifications of a focused screening exam principally because of limited access and cost [131].Although the anomalous origin and course of the left or right coronary artery has been reported to be exceedingly rare in young athletes [129], others have reported that coronary artery anomalies are the second most common association with sudden death in athletes (i.e., ≈17%) [128]. The most life-threatening anomaly is left or right coronary artery originating from the contralateral sinus of Valsalva and coursing between the aorta and proximal pulmonary artery Figure 3 [3, 132, 133].The management of the coronary anomalies is controversial [133]. If an anomalous coronary is identified or suspected further diagnostic and clinical assessment would be indicated.

    A. Echocardiogram (135). Anomalous right coronary artery (RCA) arising from a common orifice with the left main coronary artery

    Computed tomography [134]. Single right coronary artery with an inter arterial path of the left main coronary stem. Left coronary artery (white arrowheads) originates for the proximal part of the right coronary artery (black arrow) then follows an inter-arterial path between the ascending aorta and the pulmonary trunk. The white arrows indicate the inter-arterial part of the circumflex coronary artery. AO: Ascending Aorta; LA: Left Atrium LV: Left Ventricle.

    Echocardiogram[135]. Anomalous origin of he left anterior descending (LAD) coronary from the proximal right coronary artery (RCA).
    Aortic Aneurysm
    Another essential component of a focused screening CV exam is documentation of the anterior-posterior aortic diameter [e.g., leading edge to leading edge, at end-diastole [52] at the level of aortic annulus, sinuses of Valsalva, sinotubular junction, and ascending aorta. An aortic root dimension >40 mm in highly conditioned male athletes and >34 mm in female athletes is uncommon; is unlikely to represent the physiological consequences of exercise training; is most likely an expression of a pathological condition[136]; and mandates size-based surveillance [137] Table 4.Although there are multiple types of aortic aneurysms [137] there are three syndromic aortopathies of particular concern in asymptomatic athletes:Marfan syndrome [138, 139],BAV [140-142], and cystic medial necrosis [143]. The presence of any aortic valve regurgitation in a young athlete should alert the examiner to a possible structural abnormality of the aortic valve [140]. The pathophysiology and genetics of these aneurysms are similar and should be recognized as having a life-long enhanced risk of an aortic pathology [144]. In focused screening Marfan syndrome body habitus is variable and not discriminating enough to be essential. Both Marfan syndrome and cystic medial necrosis have a characteristic sinus of Val salva aneurysm (i.e., Erlenmeyer flask configuration) [139, 143] Figure 4. The aortopathy associated with BAV is different and is usually a fusi form ascending aortic aneurysm [140] Figure 5. Risk of rupture of a non-syndromic aortic aneurysm is expressed as an indexed relative size (i.e., diameter indexed to body surface area) [145-147] Table 4. However young patients particularly with a syndromic aortic aneurysm approaching 5.0 cm should be considered surgical candidate. Counseling and CV evaluation of all first-degree relatives is strongly recommended [142].In older men who have ever smoked an abdominal aortic aneurysm (AAA) should also be ruled out [148]. A ruptured AAA is usually catastrophic. Screening in women for AAA has not been shown to provide benefit [149].
    Valve Disease
    Echo/Doppleris a validated approach for evaluating both asymptomatic [150-152] and symptomatic valvular heart disease [150].Early echocardiographic screening of valve disease in the general population does not translate into reduced risk of death or cardiovascular events [153, 154].The essential objective of preparticipation athletic screening is early detection of imminent risk [48, 99, 155] and not a comprehensive echo anatomic and Doppler hemodynamic exam [155]. A multi-feature diastolic physiologic profile best reflects the magnitude of imminent risk Table 1&2 and guide to clinical care in patients with asymptomatic valve disease [156]. An athlete with an unremarkable history, normal physiologic profile, and mild anatomic valve disease may be eligible for physician monitored athletic activities.
    Congenital Heart Disease
    Congenital heart disease (CHD) is not a benign condition at
    Figure 1: Pathophysiologic Cascade.
    Figure 2: Coarctation[127].
    Figure 3: Coarctation[127].
    any age [38]. Pathophysiologic risk assessment is usually more informative than the nuances of structural abnormalities Table 1&2. Although there is no evidence that sudden death due to CHD in athletes and non-athletes has increased in frequency [119]. The prevalence of young and older CHD survivors now exceeds the incidence of pediatric CHD [157]. CV mortality is increased particularly in young persons with a history of CHD [38] ( median age at death 48.8 years; chronic heart failure (26%); sudden death (19%)). Athletic activity should be individualized and based on sound lifelong periodic pathophysiologic assessment. Patients with known CHD are not candidates for a focused screening exam [38, 90, 158]. It is recommended that all patients with known CHD have knowledgeable provider and a least one overreaching visit with a cardiologist with advance training and experience with CHD [158].
    Unanticipated Congenital Heart Disease in Athletes
    The most important attribute of a pre-participation screening exam is not diagnosis butdetermination of imminent risk and assisted decision-making [158]. The incidental finding of CHDshould not be considered a definitive test but an alert for further evaluation. Persons performing a screening examination should have a general understanding of important normal versus suspected congenital anatomy and pathophysiology [159].

    Shunt lesions are inferred in otherwise healthy individuals by increased pulmonary blood flow, asymmetric heart chamber enlargement, arrhythmias and increased pulmonary pressure.
    Figure 4: Large aneurysm of the aortic sinus in an adult patient with Marfan syndrome. The aortic sinus aneurysm is often considered analogous to an Erlenmeyer flask configuration (i.e., flat bottom, bulbous body and cylindrical neck). LA: Left Atrium; LVO: left Ventricular Outflow; MV: Mitral Valve; RVO: Right Ventricular Outflow; VS: Ventricular Septum.
    Figure 5: Left panel: Composite image of the ascending aortain a child with early morphologic features of Marfan syndrome. Note the bulbous aortic root (Erlenmeyer flask appearance). The remainder of the aorta appeared normal.
    Right panel: Bicuspid valve associated aortopathy
    Stenotic lesions are suggested by characteristic chamber remodeling and pathophysiologic risk assessment.

    Complex lesions are recognized by pathognomonicstructural variations. Essential anatomic landmarks include[74, 135].
    Apical 4-Chamber Internal Cardiac Crux
    The internal crux is the four-quadrant intersection of the atrial and ventricular septum and septal leaflets of the mitral and tricuspid valve [160] Figure 7. Many complex congenital anomalies will have an abnormality of the internal cardiac crux (e.g., Ebstein’s Anomaly, Corrected Transposition, atrioventricular canal, etc.). Patients with irregularities of the internal cardiac crux should be referred for further CV evaluation.

    The internal cardiac crux is one of the most infallible cardiac landmarks (118). The apical 4-chamber view of the heart allows identification of the crux of the heart. The morphologic tricuspid valve consistently inserts lower on the ventricular and the morphologic mitral valve inserts higher. The internal crux anatomy unambiguously confirms the commitment of the morphologic tricuspid valve to the morphologic right ventricle. Many complex congenital anomalies distort the internal cardiac crux (Ebstein Anomaly, corrected transposition).The internal cardiac crux is one of the most infallible cardiac landmarks (118).

    (Left panel) Normal internal cardiac crux of the heart: The morphologic tricuspid valve consistently inserts lower on the ventricular and the morphologic mitral valve inserts higher. The internal crux anatomy confirms the commitment of the morphologic tricuspid valve to the morphologic right ventricle. Many complex congenital anomalies distort the internal cardiac crux (e.g., Ebstein Anomaly, corrected transposition) (142,293). (Right panel) Abnormal Atrial-Ventricular Discordance:
    Figure 6: Morphology of the aortic valve.
    Figure 7: (Left panel) Normal internal cardiac crux of the heart: The morphologic tricuspid valve consistently inserts lower on the ventricular and the morphologic mitral valve inserts higher. The internal crux anatomy confirms the commitment of the morphologic tricuspid valve to the morphologic right ventricle. Many complex congenital anomalies distort the internal cardiac crux (e.g., Ebstein Anomaly, corrected transposition) (142,293). (Right panel) Abnormal Atrial-Ventricular Discordance: This patient has a complex congenital abnormality where the morphologic tricuspid valve and the morphologic right ventricle are on the left side of the heart (atrial-ventricular discordance). This patient had corrected transposition of the great arteries where the morphologic right ventricle functions under system blood pressure, which commonly leads to progressive ventricular dysfunction (morphological right ventricular failure).
    Table 4: Aorta Size in Athletes.

    (Reference)

     

    Abnormal (Athletic Aortopathy)

     

    Normal

    Recommendation (130)

    [136]

    Very Low Risk

    Mild Restriction

    Moderate Restriction

    Consider Surgery

    Male

    Female

    ≤40 mm

    ≤ 34 mm

    >40 mm

    >34 mm

    >45 mm

    To Be Determined

    ≥50 mm

    [145-147]

     

    Risk of Aorta Rupture (Indexed Diameter cm/m2)

    Risk of   Rupture

     

     

    <2.75 cm/m2

    ≈4% rupture/yr

    ≥2.75 to 4.24 cm/m2

    ≈8.5% /yr

    ≥4.25 cm/m2

    ≈20% /yr

    This patient has a complex congenital abnormality where the morphologic tricuspid valve and the morphologic right ventricle are on the left side of the heart (atrial-ventricular discordance). This patient had corrected transposition of the great arteries where the morphologic right ventricle functions under system blood pressure, which commonly leads to progressive ventricular dysfunction (morphological right ventricular failure).
    Non-Cardiovascular Causes of SCD
    A significant proportion of sport related SCD occurs in persons with known or previously unrecognized structural or functional cardiac abnormalities. However, more than 50% of sudden death in athletes is due to other causes [161]. The most common of these are suicide and drugs, which were responsible for 29% of all sudden deaths [161]. Approximately 5-15% of cardiac arrest victims are classified as autopsy negative lacking necropsy findings to establish the cause or manner of death [162]. These observations support a wider dissemination of prevention measures. First a screening test is purposefully designed to affirm an individual’s normal physiologic state [63]; a screening exam should be used for prognostication and not detection of a particular disease [12].A pathophysiologic profile will depict general risk. The risk of heat stroke [163], substance abuse [164-166],and cardiac trauma are specific to the particular situation. The risk may increase in the setting of abnormal diastolic function[167] Table 1&2. Conversely, individuals with a history of CV disease or first-degree relative are not appropriate candidates for a focused screening exam [41, 63, 66, 117, 119, 162, 168].
    References
    1. Goodreads.com. Steve Jobs' Quotable Quote. Goodreads Inc [updated NA; cited 2015 Jan 5]; Available from: http://www.goodreads.com/quotes/629613-people-think-focus-means-saying-yes-to-the-thing-you-ve
    2. Link MS, Estes NA, 3rd. Sudden cardiac death in the athlete: bridging the gaps betwe.en evidence, policy, and practice. Circulation. 2012;125(20): 2511-2516.
    3. Maron BJ. Sudden death in young athletes. N Engl J Med. 2003;349(11): 1064-1075.
    4. Corrado D, Basso C, Rizzoli G, Schiavon M, Thiene G. Does sports activity enhance the risk of sudden death in adolescents and young adults? J Am Coll Cardiol. 2003; 42(11): 1959-1963
    5. Lee WC. Selecting diagnostic tests for ruling out or ruling in disease: the use of the Kullback-Leibler distance. Int J Epidemiol. 1999;28(3):521-525.
    6. Boyko EJ. Ruling out or ruling in disease with the most sensitive or specific diagnostic test: short cut or wrong turn? Med Decis Making. 1994;14(2):175-179.
    7. Lucas RM, McMichael AJ. Association or causation: evaluating links between "environment and disease".  of the World Health Organization. 2005;83(10):792-795.
    8. Pearl J. Causal inference in statistics: An overview. Statistics Surveys. 2009; 396-146.
    9. Loscalzo J, Barabasi AL. Systems biology and the future of medicine. Wiley Interdiscip Rev Syst Biol Med. 2011;3(6):619-627.
    10. Hood L , Flores M. A personal view on systems medicine and the emergence of proactive P4 medicine: predictive, preventive, personalized and participatory. N Biotechnol. 2012;29(6):613-624.
    11. Corrado D, Basso C, Schiavon M, Pelliccia A, Thiene G. Pre-participation screening of young competitive athletes for prevention of sudden cardiac death. J Am Coll Cardiol. 2008;52(24):1981-1989.
    12. Carr N.The Glass Cage: Automation and Us. 1st Ed. New York: W.W.Norton & Company Inc; 2014.
    13. Maron BJ. Cardiovascular risks to young persons on the athletic field. Ann Intern Med. 1998;129(5):379-386.
    14. Weiner RB, Wang F, Hutter AM Jr, Wood MJ, Berkstresser B, McClanahan C, et al. The feasibility, diagnostic yield, and learning curve of portable  for out-of-hospital cardiovascular disease screening. J Am Soc Echocardiogr. 2012;25(5):568-575.
    15. Halabchi F, Seif-Barghi T, Mazaheri R. Sudden cardiac death in young athletes; a literature review and special considerations in Asia. Asian. 2011;2(1):1-15.
    16. Barabasi AL, Gulbahce N, Loscalzo J. Network medicine: a network-based approach to human disease. Nat Rev Genet. 2011;12(1):56-68.
    17. Essentialism: The Disciplined Pursuit of Less. 1st Ed. McKeown G, editor. New York: Random Hours Company; 2014.
    18. Two's Company, Three is Complexity. Johnson N, editor. Oxford, England: Oneworld; 2007.
    19. Lusis AJ, Weiss JN. Cardiovascular networks: systems-based approaches to cardiovascular disease. Circulation. 2010;121(1):157-170.
    20. Coderre S, Mandin H, Harasym PH, Fick GH. Diagnostic reasoning strategies and diagnostic success. Med Educ. 2003;37(8):695-703.
    21. Lipsitz LA. Understanding health care as a complex system: the foundation for unintended consequences. JAMA. 2012;308(3):243-244.
    22. Chang K-C, Fung R. Proceedings of the 11th international joint conference on Artificial intelligence - Volume 1. In: Node aggregation for distributed inference in Bayesian networks. Detroit: Morgan Kaufmann Publishers Inc; 1989. p. 265-270.
    23. The Naked Future: What Happens in a World that Anticipates Your Every Move? Tucker P, editor. New York: Peguin Group; 1976.
    24. Rao PS, Seib PM. Coarctation of the Aorta. [updated Sep 25, 2014; cited April 18, 2015]; Available from: http://emedicine.medscape.com/article/895502-overview
    25. Fani MF,  Stafford RS. From sick care to health care--reengineering prevention into the U.S. system. N Engl J Med. 2012;367(10):889-891.
    26. Siegel A, Etzkorn I. Simple: Conquering the Crisis of Complexicity. New York: Hachette Book Group; 2013.
    27. Smith M, Halvorson G, Kaplan G. What's needed is a health care system that learns: recommendations from an IOM report. Jama. 2012;308(16):1637-1638.
    28. Kahneman D. Thinking, Fast and Slow. 1st Ed. New York: Farrar, Straus and Giroux; 2011.
    29. Mandinov L, Eberli FR, Seiler C, Hess OM. Diastolic heart failure. Cardiovasc Res. 2000;45(4):813-825.
    30. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr. 2009;22(2): 107-133.
    31. Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, et al. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119(14): 1977-2016.
    32. Borlaug BA, Redfield MM. Diastolic and systolic heart failure are distinct phenotypes within the heart failure spectrum. Circulation. 2006;123(18):2006-2013.
    33. De Keulenaer GW, Brutsaert DL. Systolic and diastolic heart failure are overlapping phenotypes within the heart failure spectrum. Circulation. 2011;123(18):1996-2004.
    34. Lester SJ, Tajik AJ, Nishimura RA, Oh JK, Khandheria BK, Seward JB. Unlocking the mysteries of diastolic function: deciphering the Rosetta Stone 10 years later. J Am Coll Cardiol. 2008;51(7):679-689.
    35. Sen-Chowdhry S, McKenna WJ. Sudden death from genetic and acquired cardiomyopathies. Circulation. 2012; 125(12):1563-1576.
    36. Maron BJ. The 2006 American Heart Association classification of cardiomyopathies is the gold standard. Circ Heart Fail. 2008;1(1):72-76.
    37. De Ferrari GM, Schwartz PJ. Long QT syndrome, a purely electrical disease? Not anymore. Eur Heart J. 2009; 30(3):253-255.
    38. Verheugt CL, Uiterwaal CS, van der Velde ET, Meijboom FJ, Pieper PG, van Dijk AP, et al. Mortality in adult congenital heart disease. Eur Heart J. 2010;31(10):1220-1229.
    39. Maron MS, Olivotto I, Maron BJ, Prasad SK, Cecchi F, Udelson JE, et al. The case for myocardial ischemia in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2009;54(9):866-875.
    40. O'Hanlon R, Grasso A, Roughton M, Moon JC, Clark S, Wage R, et al. Prognostic significance of myocardial fibrosis in ypertrophic cardiomyopathy. J Am Coll Cardiol. 2010; 56(11): 867-874.
    41. Sekhon J. Models of Causation and Tools for Causal Inference. UC Berkeley [updated; cited]; Available from: http://sekhon.berkeley.edu/papers/causality.pdf
    42. Gibby C, Wiktor DM, Burgess M, Kusunose K , Marwick TH. Quantitation of the diastolic stress test: filling pressure vs. diastolic reserve. Eur Heart J Cardiovasc Imaging. 2013;14(3):223-227.
    43. Arques S, Roux E, Luccioni R. Current clinical applications of spectral tissue Doppler echocardiography (E/E' ratio) as a noninvasive surrogate for left ventricular diastolic pressures in the diagnosis of heart failure with preserved left ventricular systolic function. Cardiovasc Ultrasound. 2007;26;5:16.
    44. Ha JW, Oh JK, Pellikka PA, Ommen SR, Stussy VL, Bailey KR, et al. Diastolic stress echocardiography: a novel noninvasive diagnostic test for diastolic dysfunction using supine bicycle exercise Doppler echocardiography. J Am Soc Echocardiogr. 2005; 18(1): 63-68.
    45. Ha JW, Lulic F, Bailey KR, , Pellikka PA, Seward JB, Tajik AJ, et al. Effects of treadmill exercise on mitral inflow and annular velocities in healthy adults. Am J Cardiol. 2003; 91(1): 114-115.
    46. D'Ascenzi F, Cameli M, Zaca V, Lisi M, Santoro A, Causarano A, et al. Supernormal diastolic function and role of left atrial myocardial deformation analysis by 2D speckle tracking echocardiography in elite soccer players. Echocardiography. 2011; 28(3): 320-326.
    47. Firstenberg MS, Levine BD, Garcia MJ, Greenberg NL, Cardon L, Morehead AJ, et al. Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers. J Am Coll Cardiol. 2000; 36(5): 1664-1669.
    48. Loscalzo J, Kohane I, Barabasi AL. Human disease classification in the postgenomic era: a complex systems approach to human pathobiology. Mol Syst Biol. 2007; 3124.
    49. Barabasi A-L. Linked: How Everything Is Connected to Everything Else and What It Means for Business, Science, and Everyday Life. London: Penguin Books Ltd; 2003.
    50. Sebastian-Leon P, Vidal E, Minguez P, Conesa A7, Tarazona S8, Amadoz A, et al. Understanding disease mechanisms with models of signaling pathway activities. BMC Syst Biol. 2014; 8(1): 121.
    51. Seward JB, Hebl VB. Left atrial anatomy and physiology: echo/Doppler assessment. Curr Opin Cardiol. 2014; 29(5):403-407.
    52. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015; 28(1): 1-39.
    53. Pelliccia A, Maron BJ, Di Paolo FM, Biffi A, Quattrini FM, Pisicchio C, et al. Prevalence and clinical significance of left atrial remodeling in competitive athletes. J Am Coll Cardiol. 2005; 46(4): 690-696.
    54. Maron BJ, Pelliccia A. The heart of trained athletes: cardiac remodeling and the risks of sports, including sudden death. Circulation. 2006;114(15):1633-1644.
    55. Yingchoncharoen T, Agarwal S, Popovic ZB, Marwick TH. Normal ranges of left ventricular strain: a meta-analysis. J Am Soc Echocardiogr. 2013;26(2): 185-191.
    56. Saghir M, Areces M, Makan M. Strain rate imaging differentiates hypertensive cardiac hypertrophy from physiologic cardiac hypertrophy (athlete's heart). J Am Soc Echocardiogr. 2007;20(2):151-157.
    57. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997; 30(6):1527-1533.
    58. Forfia PR, Fisher MR, Mathai SC, Housten-Harris T, Hemnes AR, Borlaug BA, et al. Tricuspid annular displacement predicts survival in pulmonary hypertension. Am J Respir Crit Care Med. 2006;174(9):1034-1041.
    59. Nesto RW, Kowalchuk GJ. The ischemic cascade: temporal sequence of hemodynamic, electrocardiographic and symptomatic expressions of ischemia. Am J Cardiol. 1987; 59(7): 23C-30C.
    60. Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, et al. Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2008;29(2):270-276.
    61. Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003; 289(2):194-202.
    62. Tsang TS, Barnes ME, Gersh BJ, Takemoto Y, Rosales AG, Bailey KR, et al. Prediction of risk for first age-related cardiovascular events in an elderly population: the incremental value of echocardiography. J Am Coll Cardiol. 2003;42(7):1199-1205.
    63. Lewis GH, Sheringham J, Kalim K , Crayford T. Mastering Public Health: A Guide to Examinations and Revalidation. New York: Oxford University Press; 2008.
    64. Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014;35(39):2733-2779.
    65. Drezner JA, Ackerman MJ, Cannon BC, Corrado D, Heidbuchel H, Prutkin JM, et al. Abnormal electrocardiographic findings in athletes: recognising changes suggestive of primary electrical disease. Br J Sports Med. 2013;47(3): 153-167.
    66. Anderson JB, Grenier M, Edwards NM, Madsen NL, Czosek RJ, Spar DS, et al. Usefulness of combined history, physical examination, electrocardiogram, and limited echocardiogram in screening adolescent athletes for risk for sudden cardiac death. Am J Cardiol. 2014;114(11):1763-1767.
    67. Hill AC, Miyake CY, Grady S, Dubin AM. Accuracy of interpretation of preparticipation screening electrocardiograms. J Pediatr. 2011;159(5): 783-788.
    68. Nagueh SF, Bachinski LL, Meyer D, Hill R, Zoghbi WA, Tam JW, et al. Tissue Doppler imaging consistently detects myocardial abnormalities in patients with hypertrophic cardiomyopathy and provides a novel means for an early diagnosis before and independently of hypertrophy. Circulation. 2001;104(2):128-130.
    69. Maron BJ, Spirito P, Green KJ, Wesley YE, Bonow RO, Arce J. Noninvasive assessment of left ventricular diastolic function by pulsed Doppler echocardiography in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 1987;10(4):733-742.
    70. Rajiv C, Vinereanu D, Fraser AG. Tissue Doppler imaging for the evaluation of patients with hypertrophic cardiomyopathy. Curr Opin Cardiol. 2004;+19(5): 430-436.
    71. Afonso L, Kondur A, Simegn M, Ashutosh Niraj, Pawan Hari, Ramanjit Kaur, et al. Two-dimensional strain profiles in patients with physiological and pathological hypertrophy and preserved left ventricular systolic function: a comparative analyses.  doi: 10.1136/bmjopen-2012-001390.
    72. Minhas R. Eminence-based guidelines: a quality assessment of the second Joint British Societies' guidelines on the prevention of cardiovascular disease. Int J Clin Pract. 2007;61(7):1137-1144.
    73. Seward JB. Physiological aging: window of opportunity. JACC Cardiovasc Imaging. 2011;4(3):243-245.
    74. Eidem BW, O'Leary PW, Cetta F. Echocardiography in Pediatric and Adult Congenital Heart Disease. 2nd ED. Goolsby J, editor. Wolters Kluwer Health/Lippincott Williams & Wilkins; 2010.
    75. Menon SC, Eidem BW, Dearani JA, Ommen SR, Ackerman MJ and Miller D. Diastolic dysfunction and its histo pathological correlation in obstructive hypertrophic cardiomyopathy in children and adolescents. J Am Soc Echocardiogr. 2009;22(12):1327-1334.
    76. Nihoyannopoulos P, Dawson D. Restrictive cardiomyopathies. Eur J Echocardiogr. 2009;10(8):iii23-33.
    77.             
    78. Klein AL, Hatle LK, Taliercio CP, J K Oh, R A Kyle, Gertz MA, et al. Prognostic significance of Doppler measures of diastolic function in cardiac amyloidosis. A Doppler echocardiography study. Circulation. 1991;83(3):808-816.
    79. Rihal CS, Nishimura RA, Hatle LK, Bailey KR, Tajik AJ. Systolic and diastolic dysfunction in patients with clinical diagnosis of dilated cardiomyopathy. Relation to symptoms and prognosis. Circulation. 1994;90(6):2772-2779.
    80. Wood MJ, Picard MH. Utility of echocardiography in the evaluation of individuals with cardiomyopathy. Heart. 2004;90(6):707-712.
    81. Quinones MA. Role of Echocardiography in Predicting Onset of Heart Failure in Patients With Stable Coronary Artery DiseaseIs the Whole Greater Than the Sum of its Parts? JACC: Cardiovascular Imaging. 2009;2(1):21-23.
    82. Miyoshi H, Oishi Y, Mizuguchi Y, Iuchi A, Nagase N, Ara N, et al. Effect of an increase in left ventricular pressure overload on left atrial-left ventricular coupling in patients with hypertension: a two-dimensional speckle tracking echocardiographic study. Echocardiography. 2013;30(6):658-666.
    83. Lam CS, Roger VL, Rodeheffer RJ, Bursi F, Borlaug BA, Ommen SR, et al. Cardiac structure and ventricular-vascular function in persons with heart failure and preserved ejection fraction from Olmsted County, Minnesota. Circulation. 2007;115(15):1982-1990.
    84. Aneq MA, Engvall J, Brudin L, Nylander E. Evaluation of right and left ventricular function using speckle tracking echocardiography in patients with arrhythmogenic right ventricular cardiomyopathy and their first degree relatives. Cardiovasc Ultrasound. 2012;10(37):1476-7120.
    85. Skouri HN, Dec GW, Friedrich MG, Cooper LT. Noninvasive imaging in myocarditis. J Am Coll Cardiol. 2006; 48(10):2085-2093.
    86. Weiford BC, Subbarao VD, Mulhern KM. Noncompaction of the ventricular myocardium. Circulation. 2004; 109(24):2965-2971.
    87. Paterick TE, Tajik AJ. Left ventricular noncompaction cardiomyopathy: lessons from the past to explain a diagnostic conundrum. J Am Soc Echocardiogr. 2014;27(10):1128-1130.
    88. D'Andrea A, D'Andrea L, Caso P, Scherillo M, Zeppilli P, Calabro R. The usefulness of Doppler myocardial imaging in the study of the athlete's heart and in the differential diagnosis between physiological and pathological ventricular hypertrophy. Echocardiography. 2006;23(2):149-157.
    89. Lewis JF, Spirito P, Pelliccia A, Maron BJ. Usefulness of Doppler echocardiographic assessment of diastolic filling in distinguishing “athlete's heart” from hypertrophic cardiomyopathy. British Heart Journal. 1992;68(3):296-300.
    90. Gabrielli L, Enriquez A, Cordova S, Yanez F, Godoy I, Corbalan R. Assessment of left atrial function in hypertrophic cardiomyopathy and athlete's heart: a left atrial myocardial deformation study. Echocardiography. 2012;29(8):943-949.
    91. Maron BJ, Zipes DP. Introduction: Eligibility recommendations for competitive athletes with cardiovascular abnormalities -- general considerations. J Am Coll Cardiol. 2005;45(8):1318-1321.
    92. Galderisi M, Caso P, Severino S, Petrocelli A, De Simone L, Izzo A, et al. Myocardial diastolic impairment caused by left ventricular hypertrophy involves basal septum more than other walls: analysis by pulsed Doppler tissue imaging. J Hypertens. 1999;17(5):685-693.
    93. Takamura T, Onishi K, Sugimoto T, Kurita T, Fujimoto N, Dohi K, et al. Patients with a hypertensive response to exercise have impaired left ventricular diastolic function. Hypertens Res. 2008;31(2):257-263.
    94. Baggish AL, Wood MJ. Athlete's heart and cardiovascular care of the athlete: scientific and clinical update. Circulation. 2011;123(23):2723-2735.
    95. Seward JB, Casaclang-Verzosa G. Infiltrative cardiovascular diseases: cardiomyopathies that look alike. J Am Coll Cardiol. 2010;55(17):1769-1779.
    96. La Gerche A, Baggish AL, Knuuti J, Prior DL, Sharma S, Heidbuchel H, et al. Cardiac imaging and stress testing asymptomatic athletes to identify those at risk of sudden cardiac death. JACC Cardiovasc Imaging. 2013;6(9): 993-1007.
    97. Marijon E, Tafflet M, Celermajer DS, Florence Dumas, Marie-Cécile Perier, Hazrije Mustafic, et al. Sports-related sudden death in the general population. Circulation. 2011;124(6):672-681.
    98. Desai CS, Colangelo LA, Liu K, Jacobs DR Jr, Cook NL, Lloyd-Jones DM, et al. Prevalence, prospective risk markers, and prognosis associated with the presence of left ventricular diastolic dysfunction in young adults: the coronary artery risk development in young adults study. Am J Epidemiol. 2013;177(1):20-32.
    99. Eckart RE, Shry EA, Burke AP, McNear JA, Appel DA, Castillo-Rojas LM, et al. Sudden death in young adults: an autopsy-based series of a population undergoing active surveillance. J Am Coll Cardiol. 2011; 58(12): 1254-1261.
    100. Eagle KA, Ginsburg GS, Musunuru K, , Aird WC, Balaban RS, Bennett SK, et al. Identifying patients at high risk of a cardiovascular event in the near future: current status and future directions: report of a national heart, lung, and blood institute working group. Circulation. 2010;121(12):1447-1454.
    101. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97(18):1837-1847.
    102. Moyer VA. Screening for coronary heart disease with electrocardiography: U.S. Preventive Services Task Force recommendation statement. Ann. 2012;157(7):512-518.
    103. Chou R, Arora B, Dana T, Fu R, Walker M, Humphrey L. Screening Asymptomatic Adults for Coronary Heart Disease With Resting or Exercise Electrocardiography: Systematic Review to Update the 2004 U.S. Preventive Services Task Force Recommendation. Rockville: Agency for Healthcare Research and Quality (US). Available from:
    104. Lim LS, Haq N, Mahmood S, Hoeksema L. Atherosclerotic cardiovascular disease screening in adults: American College Of Preventive Medicine position statement on preventive practice. Am J Prev Med. 2011;40(3):381.
    105. McEvoy JW, Blaha MJ, Nasir K, Yoon YE, Choi EK, Cho IS, et al. Impact of coronary computed tomographic angiography results on patient and physician behavior in a low-risk population. Arch Intern Med. 2011;171(14): 1260-1268.
    106. McClelland RL, Chung H, Detrano R, Post W , Kronmal RA. Distribution of coronary artery calcium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2006;113(1):30-37.
    107. Taylor AJ, Cerqueira M, Hodgson JM, Daniel mark, James M, Geoffrey DR, et al. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate Use Criteria for Cardiac Computed Tomography. Journal of the American College of Cardiology. 2010; 56(22): 1864-1894.
    108. Berger JS, Jordan CO, Lloyd-Jones D, Blumenthal RS. Screening for cardiovascular risk in asymptomatic patients. J Am Coll Cardiol. 2010;55(12):1169-1177.
    109. Maron BJ, Araujo CG, Thompson PD, Fletcher GF, de Luna AB, Fleg JL, et al. Recommendations for preparticipation screening and the assessment of cardiovascular disease in masters athletes: an advisory for healthcare professionals from the working groups of the World Heart Federation, the International Federation of Sports Medicine, and the American Heart Association Committee on Exercise, Cardiac Rehabilitation, and Prevention. Circulation. 2001;103(2): 327-334.
    110. Hoffmann S, Jensen JS, Iversen AZ, Sogaard P, Galatius S, Olsen NT, et al. Tissue Doppler echocardiography improves the diagnosis of coronary artery stenosis in stable angina pectoris. Eur Heart J Cardiovasc Imaging. 2012;13(9):724-729.
    111. Ohara T, Little WC. Evolving focus on diastolic dysfunction in patients with coronary artery disease. Curr Opin Cardiol. 2010;25(6):613-621.
    112. Alsaileek AA, Osranek M, Fatema K, McCully RB, Tsang TS, Seward JB. Predictive value of normal left atrial volume in stress echocardiography. J Am Coll Cardiol. 2006;47(5):1024-1028.
    113. Greenland P, Alpert JS, Beller GA, Emelia JB, Matthew JB, Zahi AF, et al. 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults: Executive Summary. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2010;122(25):2748-2764.
    114. U.S. Preventitive Services Task Force. Screening for colorectal cancer: recommendation and rationale. Am Fam Physician. 2002;66(12):2287-2290.
    115. U.S. Preventative Services Task Force.  Breast Cancer: Screening. [updated 2009 Nov; cited 2014 Dec 16]; Available from: http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/breast-cancer-screening
    116. Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP, et al. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and Coordinating Committee. Circulation. 2002;106(3):388-391.
    117. Sudden Arrhythmia Death Syndromes Foundation.  Screening to Prevent Sudden Death. [updated 2009 Nov; cited 2015 April 18]; Available from:
    118. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm. 2013; 10(12):1932-1963.
    119. Drezner JA, Fischbach P, Froelicher V, Marek J, Pelliccia A, Prutkin JM, et al. Normal electrocardiographic findings: recognising physiological adaptations in athletes. Br J Sports Med. 2013;47(3):125-136.
    120. Maron BJ, Friedman RA, Kligfield P, Levine BD, Viskin S, Chaitman BR, et al. Assessment of the 12-lead electrocardiogram as a screening test for detection of cardiovascular disease in healthy general populations of young people (12-25 years of age): a scientific statement from the American Heart Association and the American College of Cardiology. J Am Coll Cardiol. 2014;64(14):1479-1514.
    121. Haugaa KH, Johnson JN, Bos JM, Phillips BL, Eidem BW, Ackerman MJ. Subclinical cardiomyopathy and long QT syndrome: an echocardiographic observation. Congenit Heart Dis. 2013;8(4):352-359.
    122. Simantirakis EN, Koutalas EP, Vardas PE. Arrhythmia-induced cardiomyopathies: the riddle of the chicken and the egg still unanswered? Europace. 2012;14(4):466-473.
    123. Milan A, Magnino C, Veglio F. Echocardiographic indexes for the non-invasive evaluation of pulmonary hemodynamics. J Am Soc Echocardiogr. 2010;23(3):225-239.
    124. Yared K, Noseworthy P, Weyman AE, McCabe E, Picard MH, Baggish AL. Pulmonary artery acceleration time provides an accurate estimate of systolic pulmonary arterial pressure during transthoracic echocardiography. J Am Soc Echocardiogr. 2011;24(6):687-692.
    125. Dabestani A, Mahan G, Gardin JM, Takenaka K, Burn C, Allfie A, et al. Evaluation of pulmonary artery pressure and resistance by pulsed Doppler echocardiography. Am J Cardiol. 1987;59(6):662-668.
    126. Oh JK, Seward JB, Tajik AJ. The Echo Manual. 3rd Ed. Lippincott Williams & Wilkins; 2006.
    127. Becker AE, Becker MJ, Edwards JE. Anomalies associated with coarctation of aorta: particular reference to infancy. Circulation. 1970;41(6):1067-1075.
    128. Silvilairat S, Cetta F, Biliciler-Denktas G, Ammash NM, Cabalka AK, Hagler DJ, et al. Abdominal aortic pulsed wave Doppler patterns reliably reflect clinical severity in patients with coarctation of the aorta. Congenit Heart Dis. 2008;3(6):422-430.
    129. Maron BJ, Haas TS, Doerer JJ, Thompson PD, Hodges JS. Comparison of U.S. and Italian experiences with sudden cardiac deaths in young competitive athletes and implications for preparticipation screening strategies. Am J Cardiol. 2009;104(2):276-280.
    130. Pelliccia A, Spataro A and Maron BJ. Prospective echocardiographic screening for coronary artery anomalies in 1,360 elite competitive athletes. Am J Cardiol. 1993;72(12):978-989.
    131. Wyman RA, Chiu RY, Rahko PS. The 5-minute screening echocardiogram for athletes. J Am Soc Echocardiogr. 2008;21(7):786-788.
    132. Angelini P, Vidovich MI, Lawless CE, Elayda MA, Lopez JA, Wolf D, et al. Preventing sudden cardiac death in athletes: in search of evidence-based, cost-effective screening. Tex Heart Inst J. 2013;40(2):148-155.
    133. Burke AP, Farb A, Virmani R, Goodin J, Smialek JE. Sports-related and non-sports-related sudden cardiac death in young adults. Am Heart J. 1991;121(2 Pt 1):568-575.
    134. Gersony WM. Management of anomalous coronary artery from the contralateral coronary sinus. J Am Coll Cardiol. 2007;50(21):2083-2084.
    135. Schroeder S, Achenbach S, Bengel F, Burgstahler C, Cademartiri F, de Feyter P, et al. Cardiac computed tomography: indications, applications, limitations, and training requirements: report of a Writing Group deployed by the Working Group Nuclear Cardiology and Cardiac CT of the European Society of Cardiology and the European Council of Nuclear Cardiology. Eur Heart J. 2008;29(4):531-536.
    136. Seward JB, Tajik AJ, Edwards WD, Hagler DJ. Two-dimensional Echocardiographic Atlas. New York: Springer-Verlag; 1987.
    137. Pelliccia A, Di Paolo FM, Quattrini FM. Aortic root dilatation in athletic population. Prog Cardiovasc Dis. 2012;54(5):432-437.
    138. Isselbacher EM. Thoracic and abdominal aortic aneurysms. Circulation. 2005;111(6):816-828.
    139. Yetman AT, Graham T. The dilated aorta in patients with congenital cardiac defects. J Am Coll Cardiol. 2009; 53(6):461-467.
    140. Meier JH, Seward JB, Miller FA Jr, Oh JK, Enriquez-Sarano M. Aneurysms in the left ventricular outflow tract: clinical presentation, causes, and echocardiographic features. J Am Soc Echocardiogr. 1998;11(7):729-745.
    141. Siu SC, Silversides CK. Bicuspid Aortic Valve Disease. Journal of the American College of Cardiology. 2010; 55(25):2789-2800.
    142. Losenno KL, Goodman RL, Chu MWA. Bicuspid Aortic Valve Disease and Ascending Aortic Aneurysms: Gaps in Knowledge. Cardiology Research and Practice. 2012;(2012):145202.
    143. Braverman AC. Aortic involvement in patients with a bicuspid aortic valve. Heart. 2011;97(6):506-513.
    144. Marsalese DL, Moodie DS, Lytle BW, Cosgrove DM, Ratliff NB, Goormastic M, et al. Cystic Medial Necrosis of the Aorta in Patients Without Marfan's Syndrome: Surgical Outcome and Long-Term Follow-Up. J Am Coll Cardiol. 1990; 1668-1673.
    145. Lewin MB, Otto CM. The bicuspid aortic valve: adverse outcomes from infancy to old age. Circulation. 2005; 111(7):832-834.
    146. Verma S, Siu SC. Aortic Dilatation in Patients with Bicuspid Aortic Valve. N Engl J Med. 2014;370(20):1920-1929.
    147. Davies RR, Gallo A, Coady MA, Tellides G, Botta DM, Burke B, et al. Novel measurement of relative aortic size predicts rupture of thoracic aortic aneurysms. Ann Thorac Surg. 2006;81(1):169-177.
    148. Gautier M, Detaint D, Fermanian C, Aegerter P, Delorme G, Arnoult F, et al. Nomograms for aortic root diameters in children using two-dimensional echocardiography. Am J Cardiol. 2010;105(6):888-894.
    149. Ashton HA, Buxton MJ, Day NE, Kim LG, Marteau TM, Scott RA, et al. The Multicentre Aneurysm Screening Study (MASS) into the effect of abdominal aortic aneurysm screening on mortality in men: a randomised controlled trial. Lancet. 2002;360(9345):1531-1539.
    150. Scott RA, Bridgewater SG, Ashton HA. Randomized clinical trial of screening for abdominal aortic aneurysm in women. Br J Surg. 2002;89(3):283-285.
    151. Nishimura RA, Otto CM, Bonow RO, Blasé AC, John PE, Robert AG, et al. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(23):2440-2492.
    152. Rahimtoola SH. Valvular heart disease: a perspective on the asymptomatic patient with severe valvular aortic stenosis. Eur Heart J. 2008;29(14):1783-1790.
    153. Otto CM, Burwash IG, Legget ME, Munt BI, Michelle F, Nancy LH, et al. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation. 1997;95(9):2262-2270.
    154. Lindekleiv H, Lochen ML, Mathiesen EB, Njolstad I, Wilsgaard T, Schirmer H. Echocardiographic screening of the general population and long-term survival: a randomized clinical study. JAMA Intern Med. 2013;173(17):1592-1598.
    155. Michos ED, Abraham TP. Echoing the appropriate use criteria: the role of echocardiography for cardiovascular risk assessment of the asymptomatic individual. JAMA Intern Med. 2013;173(17):1598-1599.
    156. Lung B, Gohlke-Barwolf C, Tornos P, Tribouilloy C, Hall R, Butchart E, et al. Recommendations on the management of the asymptomatic patient with valvular heart disease. Eur Heart J. 2002;23(16):1253-1266.
    157. Little WC , Oh JK. Echocardiographic evaluation of diastolic function can be used to guide clinical care. Circulation. 2009;120(9):802-809.
    158. Marelli AJ, Mackie AS, Ionescu-Ittu R, Rahme E, Pilote L. Congenital heart disease in the general population: changing prevalence and age distribution. Circulation. 2007;115(2):163-172.
    159. Warnes CA, Williams RG, Bashore TM, Child JS, Connolly HM, Dearani JA, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease). Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008; 52(23):e143-263.
    160. Krasuski RA. Cleveland Clinic CME: Congenital Heart Disease in the Adult. [updated 2010 Aug; cited 2014 Oct 28];Available from: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/congenital-heart-disease-in-the-adult/#top
    161. Seward JB, Tajik AJ, Hagler DJ, Edwards WD. Internal cardiac crux: two-dimensional echocardiography of normal and congenitally abnormal hearts. Ultrasound Med Biol. 1984;10(6):735-745.
    162. Maron BJ, Haas TS, Murphy CJ, Ahluwalia A, Rutten-Ramos S. Incidence and causes of sudden death in U.S. college athletes. J Am Coll Cardiol. 2014;63(16):1636-1643.
    163. Napolitano C, Bloise R, Monteforte N, Priori SG. Sudden cardiac death and genetic ion channelopathies: long QT, Brugada, short QT, catecholaminergic polymorphic ventricular tachycardia, and idiopathic ventricular fibrillation. Circulation. 2012;125(16):2027-2034.
    164. Shahid MS, Hatle L, Mansour H, Mimish L. Echocardiographic and Doppler study of patients with heatstroke and heat exhaustion. Int J Card Imaging. 1999;15(4):279-285.
    165. Green GA, Uryasz FD, Petr TA, Bray CD. NCAA study of substance use and abuse habits of college student-athletes. Clin J Sport Med. 2001;11(1):51-56.
    166. Deligiannis A, Bjornstad H, Carre F, Heidbüchel H, Kouidi E, Panhuyzen-Goedkoop NM, et al. ESC study group of sports cardiology position paper on adverse cardiovascular effects of doping in athletes. Eur J Cardiovasc Prev Rehabil. 2006;13(5):687-694.
    167. Christian JB, Finkle JK, Ky B, Douglas PS, Gutstein DE, Hockings PD, et al. Cardiac imaging approaches to evaluate drug-induced myocardial dysfunction. Am Heart J. 2012;164(6):846-855.
    168. Miller FA, Jr., Seward JB, Gersh BJ, Tajik AJ, Mucha P Jr. Two-dimensional echocardiographic findings in cardiac trauma. Am J Cardiol. 1982;50(5):1022-1027.
    169. Pelliccia A, Maron BJ, Culasso F, Di Paolo FM, Spataro A, Biffi A, et al. Clinical significance of abnormal electrocardiographic patterns in trained athletes. Circulation. 2000;102(3):278-284.
     
    Listing : ICMJE   

    Creative Commons License Open Access by Symbiosis is licensed under a Creative Commons Attribution 3.0 Unported License