Gregory Whyte

Exercise-Induced Cardiac Troponin Elevation Evidence, Mechanisms, and Implications

Regular physical exercise is recommended for the primary prevention of cardiovascular disease. Although the high prevalence of physical inactivity remains a formidable public health issue, participation in exercise programs and recreational sporting events, such as marathons and triathlons, is on the rise. Although regular exercise training reduces cardiovascular disease risk, recent studies have documented elevations in cardiac troponin (cTn) consistent with cardiac damage after bouts of exercise in apparently healthy individuals. At present, the prevalence, mechanism(s), and clinical significance of exercise-induced cTn release remains incompletely understood. This paper will review the biochemistry, prevalence, potential mechanisms, and management of patients with exercise-induced cTn elevations.

Ethnic Differences in Left Ventricular Remodeling in Highly-Trained Athletes : Relevance to Differentiating Physiologic Left Ventricular Hypertrophy From Hypertrophic Cardiomyopathy

OBJECTIVES The purpose of this study was to evaluate ethnic differences in left ventricular (LV) remodeling between highly-trained athletes of African/Afro-Caribbean (black) and Caucasian (white) athletes. BACKGROUND The upper limits of left ventricular hypertrophy (LVH) are established in white athletes and aid the differentiation of physiologic LVH from hypertrophic cardiomyopathy (HCM). However, there are few data regarding LV remodeling in black athletes, in whom deaths from HCM are more prevalent. METHODS Between 2003 and 2007, 300 nationally ranked black male athletes (mean age 20.5 years) underwent 12-lead electrocardiogram and 2-dimensional echocardiography. The results were compared with 150 black and white sedentary individuals and 300 highly-trained white male athletes matched for age, size, and sport. RESULTS Black athletes exhibited greater LV wall thickness and cavity size compared with sedentary black and white individuals. Black athletes had greater LV wall thickness compared with white athletes (11.3 +/- 1.6 mm vs. 10 +/- 1.5 mm; p < 0.001). In absolute terms, 54 black athletes (18%) had LV wall thickness >12 mm compared with 12 white athletes (4%), and 3% of black athletes exhibited LV wall thickness >/=15 mm compared with none of the white athletes. Black athletes with LVH displayed an enlarged LV cavity and normal diastolic function. CONCLUSIONS Black athletes develop a greater magnitude of LVH compared with white athletes; therefore, extrapolation of conclusions derived from white athletes has the potential of generating false-positive diagnoses of HCM in black athletes.

State-of-the-Art PaperExercise-Induced Cardiac Troponin Elevation: Evidence, Mechanisms, and Implications

Regular physical exercise is recommended for the primary prevention of cardiovascular disease. Although the high prevalence of physical inactivity remains a formidable public health issue, participation in exercise programs and recreational sporting events, such as marathons and triathlons, is on the rise. Although regular exercise training reduces cardiovascular disease risk, recent studies have documented elevations in cardiac troponin (cTn) consistent with cardiac damage after bouts of exercise in apparently healthy individuals. At present, the prevalence, mechanism(s), and clinical significance of exercise-induced cTn release remains incompletely understood. This paper will review the biochemistry, prevalence, potential mechanisms, and management of patients with exercise-induced cTn elevations.

Aetiology of sudden cardiac death in athletes in the United Kingdom: a pathological study

Objective: To characterise the demographics and aetiology of sudden cardiac death (SCD) in athletes referred to a tertiary cardiac pathology centre in the UK. Design: Retrospective non-case controlled analysis. Setting: Cardiac pathology centre at the National Heart and Lung Institute and Royal Brompton Hospital. Subjects: Between 1996 and 2008, the hearts of 118 athletes were referred for pathological assessment to ascertain the precise aetiology of SCD. Results: The majority of athletes (n = 113; 96%) were male and most (107; 91%) were amateurs participating predominantly in football, rugby and running. The mean (SD) age of death was 28 (12) years (range 7–59); 75% athletes were aged ⩽35 years. Most deaths (81%) occurred during or immediately after exercise. Antecedent symptoms of cardiac disease were reported in 21 (18%) subjects, and 20 (17%) had a family history of premature cardiovascular disease and/or SCD. 25 (21%) athletes had relevant past medical history which included a known history of cardiac disease. Cardiomyopathy was the commonest cause of death and accounted for 62% of all the SCDs. A significantly high proportion of athletes (23%) exhibited a morphologically normal heart. Atherosclerotic coronary disease accounted for only 3% of cases and was confined to athletes aged >35 years. Conclusions: SCD in sport is largely due to clinically silent cardiomyopathies or primary electrical disorders (morphologically normal heart). Antecedent symptoms and family history are absent in over 80% of cases, and therefore clinical screening with health questionnaires will fail to identify most athletes with potentially sinister cardiac disorders.

The exercise-induced growth hormone response in athletes.

Human growth hormone (hGH) is secreted in a pulsatile fashion, generally following a circadian rhythm. A number of physiological stimuli can initiate hGH secretion, the most powerful, non-pharmacological of which are sleep and exercise. hGH has many varied roles throughout life, from growth itself, including the turnover of muscle, bone and collagen, to the regulation of selective aspects of metabolic function including increased fat metabolism and the maintenance of a healthier body composition in later life.The exercise-induced growth hormone response (EIGR) is well recognised and although the exact mechanisms remain elusive, a number of candidates have been implicated. These include neural input, direct stimulation by catecholamines, lactate and or nitric oxide, and changes in acid-base balance. Of these, the best candidates appear to be afferent stimulation, nitric oxide and lactate.Resistance training results in a significant EIGR. Evidence suggests that load and frequency are determining factors in the regulation of hGH secretion. Despite the significant EIGR induced by resistance training, much of the stimulus for protein synthesis has been attributed to insulin-like growth factor-1 with modest contributions from the hGH-GH receptor interaction on the cell membrane.The EIGR to endurance exercise is associated with the intensity, duration, frequency and mode of endurance exercise. A number of studies have suggested an intensity ‘threshold’ exists for EIGR. An exercise intensity above lactate threshold and for a minimum of 10 minutes appears to elicit the greatest stimulus to the secretion of hGH. Exercise training above the lactate threshold may amplify the pulsatile release of hGH at rest, increasing 24-hour hGH secretionThe impact of chronic exercise training on the EIGR remains equivocal. Recent evidence suggests that endurance training results in decreased resting hGH and a blunted EIGR, which may be linked to an increased tissue sensitivity to hGH.Whilst the potential ergogenic effects of exogenous GH administration are attractive to some athletes, the abuse of GH has been associated with a number of pathologies. Identification of a training programme that will optimise the EIGR may present a viable alternative.Ageing is often associated with a progressive decrease in the volume and, especially, the intensity of exercise. A growing body of evidence suggests that higher intensity exercise is effective in eliciting beneficial health, well-being and training outcomes. In a great many cases, the impact of some of the deleterious effects of ageing could be reduced if exercise focused on promoting the EIGR.This review examines the current knowledge and proposed mechanisms for the EIGR, the physiological consequences of endurance, strength and power training on the EIGR and its potential effects in elderly populations, including the aged athlete.

Efficacy of personal symptom and family history questionnaires when screening for inherited cardiac pathologies: the role of electrocardiography

Aims: This study sought to confirm the efficacy of using resting 12-lead ECG alongside personal symptom and family history questionnaires and physical examination when screening for diseases with the potential to cause sudden cardiac death in the young. Methods and results: 1074 national and international junior athletes (mean age 15.8 (SD 0.7) years, range 10 to 27) and 1646 physically active schoolchildren (16.1 (SD 2.1) years, range 14 to 20) were screened using personal and family history questionnaires, physical examination and resting 12-lead ECG. Nine participants with a positive diagnosis of a disease associated with sudden cardiac death were identified. None of the participants diagnosed with a disease associated with sudden cardiac death were symptomatic or had a family history of note. Conclusion : Family history and personal symptom questionnaires alone are inadequate to identify people with diseases associated with sudden cardiac death. Use of the 12-lead ECG is essential when screening for cardiac pathology in the young.

Ethnic Differences in Physiological Cardiac Adaptation to Intense Physical Exercise in Highly Trained Female Athletes

Background— Ethnicity is an important determinant of cardiovascular adaptation in athletes. Studies in black male athletes reveal a higher prevalence of electric repolarization and left ventricular hypertrophy than observed in white males; these frequently overlap with those observed in cardiomyopathy and have important implications in the preparticipation cardiac screening era. There are no reports on cardiac adaptation in highly trained black females, who comprise an increasing population of elite competitors. Methods and Results— Between 2004 and 2009, 240 nationally ranked black female athletes (mean age 21±4.6 years old) underwent 12-lead ECG and 2-dimensional echocardiography. The results were compared with 200 white female athletes of similar age and size participating in similar sports. Black athletes demonstrated greater left ventricular wall thickness (9.2±1.2 versus 8.6±1.2 mm, P<0.001) and left ventricular mass (187.2±42 versus 172.3±42 g, P=0.008) than white athletes. Eight black athletes (3%) exhibited a left ventricular wall thickness >11 mm (12 to 13 mm) compared with none of the white athletes. All athletes revealed normal indices of systolic and diastolic function. Black athletes exhibited a higher prevalence of T-wave inversions (14% versus 2%, P<0.001) and ST-segment elevation (11% versus 1%, P<0.001) than white athletes. Deep T-wave inversions (−0.2 mV) were observed only in black athletes and were confined to the anterior leads (V1 through V3). Conclusions— Systematic physical exercise in black female athletes is associated with greater left ventricular hypertrophy and higher prevalence of repolarization changes than in white female athletes of similar age and size participating in identical sporting disciplines. However, a maximal left ventricular wall thickness >13 mm or deep T-wave inversions in the inferior and lateral leads are rare and warrant further investigation.

Prevalence of hypertrophic cardiomyopathy in highly trained athletes relevance to pre-participation screening.

OBJECTIVES This study sought to determine the prevalence of hypertrophic cardiomyopathy (HCM) in elite athletes. BACKGROUND Hypertrophic cardiomyopathy is considered to be the most common cause of exercise-related sudden death in young athletes. The prevalence of HCM in elite athletes has never been reported but has important implications with regard to pre-participation screening for the disorder. METHODS Between 1996 and 2006, 3,500 asymptomatic elite athletes (75% male) with a mean age of 20.5 +/- 5.8 years (range 14 to 35 years) underwent 12-lead electrocardiography and 2-dimensional echocardiography. None had a known family history of HCM. RESULTS Of the 3,500 athletes, 53 (1.5%) had left ventricular hypertrophy (mean 13.6 +/- 0.9, range 13 to 16), and of these 50 had a dilated left ventricular cavity with normal diastolic function to indicate physiological left ventricular hypertrophy. Three (0.08%) athletes with left ventricular hypertrophy had a nondilated left ventricular cavity and associated deep T-wave inversion that could have been consistent with HCM. However, none of the 3 athletes had any other phenotypic features of HCM on further noninvasive testing and none had first-degree relatives with features of HCM. One of the 3 athletes agreed to detrain for 12 weeks, which showed resolution of electrocardiography and echocardiographic changes confirming physiologic left ventricular hypertrophy. CONCLUSIONS The prevalence of HCM in highly trained athletes is extremely rare. Structural and functional changes associated with HCM naturally select out most individuals from competitive sports. Screening athletes with echocardiography is not cost effective. However, electrocardiography is useful in selecting out those individuals who may have pathological left ventricular hypertrophy for subsequent echocardiography.

Cardiac fatigue following prolonged endurance exercise of differing distances.

PURPOSE Recent echocardiographic studies have reported cardiac dysfunction following ultra-endurance exercise in trained individuals. The duration of exercise required to elicit cardiac dysfunction and the mechanisms underlying this phenomenon have not been fully elucidated. The aim of the present study was to examine the presence of cardiac dysfunction following a half-Ironman and Ironman triathlon in trained individuals. METHODS 14 male triathletes (age: 32 +/- 5 yr; height: 180 +/- 8 cm; body mass: 75 +/- 9 kg) completed a half-Ironman triathlon. Following a 4-wk period, 10 of the original 14 triathletes completed an Ironman triathlon. All triathletes were assessed using ECG, echocardiography, and blood analysis pre-, immediately post-, and 48 h postrace for both distances. RESULTS Echocardiographic results indicated diastolic and systolic left ventricular dysfunction, for both race distances, which were associated with altered relaxation characteristics and a reduced inotropic contractility, respectively. Following 48-h recovery, all echocardiographic measures were similar to resting values. Creatine kinase MB (CKMB) was significantly elevated immediately postrace for both distances; however, it accounted for less than 5% of the total CK value and in the presence of an elevated total CK and CKMM implied that the elevated CKMB was noncardiac in origin. Troponin-T, however, was significantly elevated immediately postrace for both distances and returned to normal following 48-h recovery indicating myocardial damage. CONCLUSIONS Ironman and half-Ironman competition resulted in reversible abnormalities in resting left ventricular diastolic and systolic function. Results suggest that myocardial damage may be, in part, responsible for cardiac dysfunction, although the mechanisms responsible for this cardiac damage remain to be fully elucidated.

Impact of marathon running on cardiac structure and function in recreational runners

The present study examined the relationship between LV (left ventricular) function, markers of cardiac-specific damage and markers of oxidative stress in recreational runners following a marathon. Runners (n=52; 43 male and nine female; age, 35+/-10 years; height, 1.74+/-0.08 m; body mass, 75.9+/-8.9 kg) were assessed pre- and immediately post-marathon. LV function was assessed using standard M-mode two-dimensional Doppler echocardiography and TDI (tissue-Doppler imaging) echocardiography. Serum was analysed for cTnT (cardiac troponin-T), TEAC (Trolox equivalent antioxidant capacity; a measure of total antioxidant capacity), MDA (malondealdehyde) and 4-HNE (4-hydroxynonenal). A strong relationship was observed between standard and TDI echocardiography for all functional measures. Diastolic function was altered post-marathon characterized by a reduction in E (peak early diastolic filling: 0.79+/-0.11 compared with 0.64+/-0.16 cm/s; P<0.001), an increase in A (peak late diastolic filling: 0.48+/-0.11 compared with 0.60+/-0.12 cm/s; P<0.001) and a resultant decrease in E/A (ratio of E to A; 1.71+/-0.48 compared with 1.10+/-0.31; P<0.001). Ejection fraction remained unchanged post-marathon. Thirty-two runners presented with cTnT values above the lower limit of detection for the assay (0.01 microg/l), and 20 runners presented post-marathon with cTnT values above the acute myocardial infarction cut-off value (0.05 microg/l). No significant correlations were observed between cTnT and any functional measurements. MDA (2.90+/-1.58 compared with 3.59+/-1.47 micromol/l) and TEAC (1.80+/-0.12 compared with 1.89+/-0.21 mmol/l) were significantly increased post-marathon, but were unrelated to changes in function or cTnT. In conclusion, the present study demonstrated a reduction in diastolic function and widespread evidence of minimal cardiac damage following a marathon in recreational runners. The mechanism(s) underpinning the altered function and appearance of cTnT appear unrelated to reactive oxygen species.