ATHLETE’S HEART

The athlete’s heart is a set of morphological and functional characteristics that develop over time due to sports training. These adaptive changes result in increase in cardiac work efficiency and economy. They are manidested as cardiac muscle hypertrophy and dilation, with accompanying angiogenesis and slower heart rate, that are influenced by variable regulatory systems and genetic predisposition. The problem of sudden cardiac death in athletes, which persists despite numerous activities aimed at prevention, creates the need for a better definition of the athlete`s heart, especially in terms of its differentiation from certain pathological conditions. This is of particular importance in the context of cardiac electrical activity. Right heart adaptations, hormonal regulatory mechanisms and the effects of nonphysiological adaptations during training, that may lead to pathologic alterations direction, are all relevant in the investigation of adverse cardiac events in athletes. In order to prevent sudden cardiac death in athletes, it is necessary to examine competitive athletes as well as apparently health individsuals who recreationally exercise at a high volume. There are guidelines for mass screening and individual examinations, for all age groups and both genders, as well as for public service staff who require intense physical activity during their occupation. Both American and European recommendations require a detailed anamnesis and physical examination, whereas European, apart from that, require initial electrocardiography. The implementation of additional tests is necessary if the existence of any underlying pathophysiologic process is suspected. Checks should be performed before engaging in sports activities, as well as during training and competition periods.


THE CONCEPT OF ATHLETE'S HEART
To safely and efficiebtly perform physical activity, homeostasis and the integrated action of several physiologic systems is necessary.The cardiovascular system is particularly exposed to major and crucial changes during intense and prolonged physical activity and certain competitive sports.Morphological, functional and electrophysiological changes that occurin heart muscle that occur as a result of chonic, high-volume exercise training has been termed "athletic heart syndrome" or "athlete's heart" (Levine, 2001;Sharma, Merghani, Mont, 2015).
with some pathological conditions that can significantly increase the risk for sudden cardiac death.Research suggests that besides the clinically well-defined "gray zone" between physiology and pathology of the heart, a well-organised forensic database is needed, for the more transparent epidemiology of sudden cardiac death, in order to improve prevention of this event (Oliva et al, 2017).This problem is even more complex considering that the changes that characterize the athlete's heart are highly variable and depend largely on individual characteristics, sports discipline and level of training (Kaşıkcıoğlu, 2011).
Today, the athlete's heart is defined as a set of morphological and functional characteristics of the heart that develop over time under the influence of intense physical training over a prolonged period.Adapations include enlarged cardiac cavities and thickness of the walls of the heart as well as a decline in heart rate, which results in an increased in cardiac funcition during both rest and exercise (Popovic, Mazic, Djordjevic-Dikic, 2004).
The goal of this review is to present a more detailed overview of morpho-functional adaptive changes in the heart of athletes, in regards with the latest findings, as well as to revew the latest recommendations for screening of athletes presented by the European and American Cardiologists Association as well as the International Olympic Committee for early detection of cardiovascular abnormalities that can lead to sudden cardiac death.

GENESIS OF ADAPTIVE MORPHO-FUNCTIONAL CHANGES IN ATHLETE'S HEART
Although the athlete's heart can be seen as myocardial hypertrophy (Maron, 2015), it is very important to define precisely the morphological characteristics of the heart, since these changes can also develop as a result of an unrecognized pathological condition (Beaudry, Haykowsky, Baggish, La Gerche, 2016).During the process of formation of an athlete's heart, the role of intensity, duration and type of exercise training is important, but the influence of ethnicity, years and a gender cannot be neglected (Beaudry, Haykowsky, Baggish, La Gerche, 2016).Mitchell and colleauges proposed the classification of sports based on the amount of static and dynamic training component, which has been modified in recent years to classify sports into four groups: 1) skills; 2) strength; 3) endurance; and 4) mixed disciplines (Mitchell, Haskell, Snell, Van Camp, 2005; Eijsvogels, Fernandez, Thompson, 2016).In each of these categories, different cardiac adapations and characteristics can be expected (Pluim, 1999).
Adaptive changes in the heart of athletes result in an increased strength of cardiac contraction with, depending on type of training, variable effects on stroke volume and cardiac output.Static training leads to increased strength of cardiac contraction but has less effect on cardiac output (Levine, 2001; Serneri, Boddi, Modesti et al, 2001), while dynamic training significantly increases cardiac output in order to overcome peripheral resistance in the blood vessels with purpose of effective perfusion of the active skeletal musculature.When performing static exercises, diastolic arterial pressure increases, while changes in systolic pressure are minimal.While by performing dynamic exercises, mean arterial pressure is constant or increases slightly (Levine, 2001).Thus, predominantly static training usually causes the so-called concentric adaptation, which involves myocardial hypertrophy without a noticeable dilatation of the heart cavities (Nakamura, Soares-Caldeira, Laursen, Polito, Leme, Buchheit, 2009), thereby increasing the mass/volume ratio of the heart (Toufan, Kazemi, Akbarzadeh, Ataei, Khalili, 2012; Boettger et al, 2010).Consequences of dynamic training because of increased heart rate, are enlarged heart cavities with minor thickening of the heart walls.(Oxborough et al, 2016).
In normal conditions, with preserved heart compliance, contractility and subsequent filling (pressure in systemic circulation), the main factors effecting the pumping ability of the heart are the effective filling pressure and chamber siffness at the end of diastole.The pump capacity of the heart, depends on the length of the smallest contractile heart unit -sarcomeres before contraction, which is directly related to the chamber filling.If the chambers are filled with more blood before contraction, sarcomeres grow to a certain level (2.25 microns), and according to Frank -Starling's law, there is an increase in stroke volume Contractility of the heart also depends on the composition of the myocardium (mass and distribution of actin and myosin fibers) and the effects of humoral factors and myocardial exposure to stress.(Popovic, el al, 2007).The most important humoral factor, activity, and both are triggered during exercise.Capillary maintenance and prevention of apoptosis, fibrosis and myocardial dysfunction due to exercise by various regulatory mechanisms are of importantance in the athlete heart adaptations.(Silva et al, 2014).By Lapace's law, the heart has better work efficiency if it is hypertrophic, dilated and has a lower heart rate (Puffer, 2001), all of which are key physiological adaptive consequences of physical activity; these changes may also initiate pathological processes.There are two types of compensatory factors that affect the efficiency of cardiac work, one is favorable, while the other is detrimental (Popovic et al, 2001).For example, increasing thickness of the wall of the left ventricle leads to a reduction in compliance and therefore increases stiffness of the chamber (Popovic et al, 2007).On the other hand, myocardial stiffness is directly proportional to wall stress (Popovic et al, 2011).Further constant strain on the left ventricle favors the onset of cardiac insufficiency, as it favors the beginning of remodeling and dilatation of the heart muscle (Popovic et al, 2007).
All this suggests that cardiac adaptation to the chronic physical stress of high-volume exercise training and sports is a very complex process, involving different regulatory mechanisms, with a very narrow adaptive window which enables increased work efficiency.Any non-physiological manipulation during the training process further complicates these processes and may turn them in the pathological direction (overtraining, doping, dehydration, etc.), with potential fatal consequences.

MORPHO-FUNCTIONAL CHANGES IN ATHLETE'S HEART
Most studies show that the end-diastolic heart diameter of athletes in relation to the sedentary population is increased by 10% (Pluim, 1998).A key finding ina study performed by Pelliccia et al. was that more than 10% of athletes had left-ventricular end-diastolic dimensions greater than 60 mm, a population of athletes who need to be further evaluated in terms of dignosing dilatative cardiomyopathy, a condition that can lead to sudden cardiac death.
The left-ventricular wall thickness up to 13 mm, with the presence of symmetrical hypertrophy, is considered to most likely be characteristic of an athlete's which leads to hypertrophy of cardiomyocytes and, consequently, changes in the morphology of the athlete's heart, is an insulin stimulating factor in cooperation with norepinephrine.The main carrier of sympathetic activity, noradrenaline, is highly pronounced during high-volume exercise training and has inotropic effects through increased calcium influx.(Serneri, Boddi, Modesti et al, 2001).
In untrained individuals at rest, the parasympathetic component dominates, which reduces heart rate as well as the rate of conduction.The high tonus of the vagal nerve is initially reduced with increased physical effort and the dominance of sympathetic activity begins.Athletes whose training is primarily dynamic, stimulate the development of a stronger vagal tone (Dong, 2016), which postpones the excessive increase in the sympathetic component during exercise.Many studies point to the general parasympathetic dominance of the sympathetic regulatory component in athletes, which leads to morpho-functional changes in the heart (Dong, 2016; Naylor, George, O'Driscoll, Green, 2008;Fagard, 1992).Consequently, the regulatory range of cardiac rhythm, contractility, diastolic function and blood pressure is increased.
Although it has been shown that the athletic heart will inevitably develop in high-level athletes, the degree of morphological and functional changes may vary from person to person.For example, carriers of the adrenocorticotropic receptor polymorphism (ACTHRP) have a reduced number of cardiac contractions per minute, enlarged mass and left chamber diameter, better systolic function, and decreased left ventricular compliance.It has been proven that AC-THRP has a predictive role in terms of the structure and function of the heart, indicating that the activation of the hormonal stress system and the sensitivity to stress hormones influence cardiac remodeling.Also, the correaliton between stress hormone and body composition has been found.Thus, adaptive changes in the heart of athletes are partly mediated by the repetitive and prolonged activation of the hypothalamic-pituitary-adrenal axis, which is influenced by genetic predisposition (Popovic et al, 2014).
In addition to all of the above factors, cardiac adaptation leads to functional and structural changes in the coronary circulation, resulting in improved work efficiency.(Dickhuth, Röcker, Mayer, König, Korsten-Reck, 2004).Recent research shows that the kininkallikrein system as well as angiogenesis has a role inprotecting the heart from excessive sympathetic heart.When considering left chamber wall thickness, it is important to rule out the existence of hypertrophic cardiomyopathy, a genetic disease which could be the cause of sudden cardiac death during sport events.Walls thicker than 13 mm, with an asymmetry that implies greater septal thickeness, favors this diagnosis (Lee et al, 2013).Left -ventricular wall thickness-to-diameter ratio is an important parametar, and normally should be between 0.3 and 0.45 in the athlete (Pelliccia et al, 1999).Not only does this parameter indicate hypertrophic cardiomyopathy or dilatative cardiomyopathy, whether its increased or decreased respectively, but also provides information on whether remodeling of the left ventricle is concentric or eccentric.(Pelliccia et al, 1999;Douglas et al, 1997).However, it should be kept in mind that in a small number of athletes (about 2%), a increased thickness-to-diameter ratio could be physiologic and normal (Douglas et al, 1997).
In trained athletes, left-ventricular mass is 45-50% higher compared to the sedentary population; only a small number of these athletes (≈15-20%) present with values that could indicate hypertrophic cardiomyopathy (Thomas, Douglas, 2001).If this parameter is observed in relation to body fat or body surface area, this percentage is reduced further.Interestingly, female athletes show significantly less heart mass enlargement than males (Pelliccia et al, 1991).Pelliccia et al. has also found that there is a disproportionately higher risk of sudden cardiac death in female athletes compared to males, which does not correlate simply with lesser participation in sports, nor with less intensity and duration of training.These authors emphasize the importance of understanding the genetic and/or hormonal mechanisms which lower the risk of acute cardiac events in women (Pelliccia, Adami, 2017).
In the past decade, several studies have analyzed right-ventricular hypertrophy as a result of adaptation to regular physical activity.The methods of measurement used for these studies are echocardiography (D' Andrea et al, 2013; Oxborough et al, 2012; Teske et al, 2009) or nuclear magnetic resonance (Perseghin et al, 2007;Prakken et al, 2011).The use of tissue Doppler imaging brings new possibilities in assessing systolic adaptive changes to the right ventricle and predicting its functional capacity, which could lead to better quantification of the morpho-functional changes in athlete's hearts (Popovic et al., 2011.)Considering morphological and functional specificity of the right chamber, it`s evalulation is challeng-ing.The diagnosis of arrhythmogenic cardiomyopathy or dysplasia is particularly hard, both conditions could sudden cardiac death in athletes (Corrado et al, 2010).Greater morphological and less functional adaptation of the right ventricle in contrast to the left ventricle in athletes can be explained by greater resistance in the systemic compared to pulmonary circulation.Morphological changes in the right ventricle increase its efficacy, so further functional changes are not of major importance (Major, Csajági, Kneffel, Kováts, Szauder, Sidó, Pavlik, 2015).
The cardiac atriums in male and female athletes also undergo remodeling, with minor or major alterations compared to the sedentary population.The right atrium undergoes greater changes in size in male athletes, while biatrial changes are more pronounced in female athletes (Sanchis et al, 2017).
Morphological changes in the heart of the athletes are also the result of its functional changes.It has already been mentioned that the athlete's heart has a reduced rate and increased work efficiency.Reduced heart rate in athletes is related to increasedparasympathetic tonus, enlarged cardiac cavities and increased cardiac contraction efficiency, which allow for a lower number of heart cycles to fulfill oxygen needs at rest.Experimental findings suggest a regulatory role ofbrain natriuretic peptide (BNP).BNP increases heart rate and electrical conductivity by stimulating ionic currents in the sinoatrial node and atrial myocardium.Moreover, correlation of maximal cardiac frequency with increased BNP during physical activity has been shown in previous studies.In addition, BNP has been shown to correlate with systolic parameters of the left and right ventricles, as well as the diameter of the right atrium in athletes.Recent studies also show a correlation between BNP and lung function parameters in athletes.Collectivelty, evidence indicates BNP is a significant regulatory factor that coordinates heart and lung adapations in athletes (Popovic et al, 2013).

ELECTROPHYSIOLOGICAL CHARACTERISTICS OF ATHLETE'S HEART
There is a small percentage of athletes (≈3-5%) undergo changes in the electrical activity of the heart, which are decected by electrocardiography (ECG) (Calore et al, 2015).These changes depend on the type of sport, gender and age.They are reported in athletes whose training is predominantly dynamic.A frequent finding among athletes up to 16 years of age is the T-wave inversion in V1-V4, which disappears with aging (Sharma, Merghani, Mont, 2015).When we observe ECG records in terms of gender, we notice that inmale athletes aged 12 to 40, only 50-60% of cases have normal findings, while female athletes of the same age the percentage is even higher -75-80% (Pelliccia, Maron, Culasso, Spataro, Caselli, 1996).
Changes in the ECG that occur in athletes can be divided into two groups.The first group contains changes that are common, their appearance is related to physical activity, and are considered normal findings (sinus bradycardia, AV block I degree, Mobitz I, early repolarization, sinus arrhythmia, etc).The second group contains less frequent ECG varieties that are not only dependent on physical activity, but can also be found in some pathological conditions (T wave inversion, complete block of the left branch, the occurrence of pathological Q teeth, depression of ST segment, etc.) (Sharma et al 2017).It is necessary that athletes with abnormal ECG findings, and with an initially normal physical examination, are monitored on a regular basis.(Sharma et al, 2017).

ATHLETE SCREENING
Since the athlete's heart may morphologically mask the various pathological conditions, which can lead to tragic outcomes, it is necessary to monitor both athletes and those individuals participating in high-volume physical activityon a regular basis.These checks should be carried out before engaging in sports activities, during the training period and during competition.Screening for use of prohibited substances is of great importance (Hainline et al, 2016).The role of sports cardiologists in the planning, implementation and improvement of initial examination is crucial.Initial examinations provide valuable information about preferences for particular sports disciplines, provide an insight into cardiovascular function before engaging in sports, and warn of possible limitations.
Preparticipation screening is needed for the early detection of pathological conditions that can lead to sudden cardiac death, in both older and younger athletes.For certain age groups, such as college students, there are recommendations in this regard.In this group of athletes, it is recommended that the screening conduct within a preexisting team with dedicated team physicians, trainers, and oncampus health centers (Maron BJ et al, 2007).Unfortunately, there are still no guidelines on preparticipation screening of high school athletes.The responsibility for obtaining medical clearance usually rests with the individual high school student-athlete to identify a healthcare provider.In this age group screening usually consists of a history and physical examination, is customary.
The International Olympic Committee recommendations on periodic systematic reviews are as follows.Appearance of sudden cardiac deaths by the aged 50, as well as the existence of cardiovascular diseases in the family history.In a personal history, pay attention to the occurrence of heart palpitations, irregular heartbeat, syncope, chest pain or discomfort, shortness of breath or fatigue.In physical examination, look for features suggestive of Marfan syndrome, pathological pulsations, heart murmur, irregular heart rhythm, high blood pressure.The 12lead ECG should be recorded on a non-training day, during rest.(IOC, 2009) Recommendations were given at the 36th Bethesda Conference in 2005 (36th Bethesda Conference, 2005), including mass screenings and individual reviews, for all age groups and both sexes, as well as for individuals who have intense occupational physical efforts (police officers, firefighters, etc.).According to these recommendations, athletes should be examined before engaging in sports, and every two years of sport participation thereafter.These checks must be more frequent (2-3 times a year) during periods of intense competition.Recommendations state that the review consists of non-invasive tests that involve the collection of data of personal and family history and physical examination with measurement of arterial blood pressure.In the context of personal history, questions regarding chest pain, previously detected heart murmurs or increased pressure, syncopes and unexplained fatigue and included.Family history focuses on the presence of sudden deaths in the family and cardiovascular disease in relatives under 50 years of age.An objective examination includes heart auscultation and pulse palpation, primarily femoral pulse.
When it comes to mass screening programs, it's interesting to note that the 36th Bethesda guide lines initially do not recommend the use of electrocardiography, echocardiography, and ergo spirometry because of cost limitations, although it is known that more than half of sudden cardiac deaths can be prevented by an analysis of electrocardiograhy.However, the recommendations state that if there is any doubt about the existence of a disease, pathological change or disorder, these latter tests must be carried out.It is recommended that national standards should be developed, due to different economic models in different countries, and due to the need for early detection of hidden illnesses.These routine tests according to valid recommendations can be carried out by doctors as well as by medical technicians, who passed organized courses that would enable them to perform this activity.
The On the other hand, the American Association of Cardiologists recommends that doctors use screening guides such as "the American Heart Association's 14 points screening guidelines" as a part of extensive history and physical examination in order to detect congenital or other cardiovascular disorders.Standardization of different forms of questionnaires, used as guidelines by physicians for examining athletes in high schools and faculties, is recommended.The standard ECG, as a screening test, can be considered in relatively small groups of young, healthy people aged 12 to 25 who are at risk, and may not necessarily be limited to athletes who compete.Participation of doctors and adequate quality control is mandatory (Maron et al, 2015).Similar to European guidelines, American recommendations require conduction of additional tests if there is any suspicion of cardiovascular disease or structural abnormalities.
Monitoring the recommendations for medical care of athletes is necessary in terms of setting clear boundaries between physiological adaptive changes and pathological changes as a consequence of disease.Only in this way can we reduce the incidence of tragic events in athletes, who, unfortunately, are still very common.