David Oxborough

Diverse patterns of myocardial fibrosis in lifelong, veteran endurance athletes

This study examined the cardiac structure and function of a unique cohort of documented lifelong, competitive endurance veteran athletes (>50 yr). Twelve lifelong veteran male endurance athletes [mean ± SD (range) age: 56 ± 6 yr (50-67)], 20 age-matched veteran controls [60 ± 5 yr; (52-69)], and 17 younger male endurance athletes [31 ± 5 yr (26-40)] without significant comorbidities underwent cardiac magnetic resonance (CMR) imaging to assess cardiac morphology and function, as well as CMR imaging with late gadolinium enhancement (LGE) to assess myocardial fibrosis. Lifelong veteran athletes had smaller left (LV) and right ventricular (RV) end-diastolic and end-systolic volumes (P < 0.05), but maintained LV and RV systolic function compared with young athletes. However, veteran athletes had a significantly larger absolute and indexed LV and RV end-diastolic and systolic volumes, intraventricular septum thickness during diastole, posterior wall thickness during diastole, and LV and RV stroke volumes (P < 0.05), together with significantly reduced LV and RV ejection fractions (P < 0.05), compared with veteran controls. In six (50%) of the veteran athletes, LGE of CMR indicated the presence of myocardial fibrosis (4 veteran athletes with LGE of nonspecific cause, 1 probable previous myocarditis, and 1 probable previous silent myocardial infarction). There was no LGE in the age-matched veteran controls or young athletes. The prevalence of LGE in veteran athletes was not associated with age, height, weight, or body surface area (P > 0.05), but was significantly associated with the number of years spent training (P < 0.001), number of competitive marathons (P < 0.001), and ultraendurance (>50 miles) marathons (P < 0.007) completed. An unexpectedly high prevalence of myocardial fibrosis (50%) was observed in healthy, asymptomatic, lifelong veteran male athletes, compared with zero cases in age-matched veteran controls and young athletes. These data suggest a link between lifelong endurance exercise and myocardial fibrosis that requires further investigation.

Changes in vascular and cardiac function after prolonged strenuous exercise in humans

Prolonged exercise has been shown to result in an acute depression in cardiac function. However, little is known about the effect of this type of exercise on vascular function. Therefore, the purpose of the present study was to investigate the impact of an acute bout of prolonged strenuous exercise on vascular and cardiac function and the appearance of biomarkers of cardiomyocyte damage in 15 male (32 +/- 10 yr) nonelite runners. The subjects were tested on two occasions, the day before and within an hour of finishing the London marathon (229 +/- 38 min). Function of the brachial and femoral arteries was determined using flow-mediated dilatation (FMD). Echocardiographic assessment of cardiac strain, strain rate, tissue velocities, and flow velocities during diastole and systole were also obtained. Venous blood samples were taken for later assessment of cardiac troponin I (cTnI), a biomarker of cardiomyocyte damage. Completion of the marathon resulted in a depression in femoral (P = 0.04), but not brachial (P = 0.96), artery FMD. There was no change, pre- vs. postmarathon, in vascular shear, indicating that the impaired femoral artery function was not related to hemodynamic changes. The ratio of peak early to atrial radial strain rate, a measure of left ventricular diastolic function, was reduced postmarathon (P = 0.006). Postrace cTnI was elevated in 12 of 13 runners, with levels above the recognized clinical threshold for damage in 7 of these. In conclusion, when taken together, these data suggest a transient depression in cardiac and leg vascular function following prolonged intensive exercise.

A prospective randomised longitudinal MRI study of left ventricular adaptation to endurance and resistance exercise training in humans

Non‐Technical Summary  This is the first study, to our knowledge, to use cardiac MRI before and after intensive and closely supervised resistance and endurance exercise training in humans. There is a long held belief that these different forms of training induce ‘concentric’ and ‘eccentric’ adaptation of the heart, but this concept is based on echocardiographic assessments and cross‐sectional comparison of different types of elite athletes. Our findings, using highly sensitive MRI methodology, suggest that concept may need to be reconsidered. This study is of fundamental importance to the understanding of the impact of exercise on human cardiac morphology and physiology.

Dilatation and Dysfunction of the Right Ventricle Immediately After Ultraendurance Exercise Exploratory Insights From Conventional Two-Dimensional and Speckle Tracking Echocardiography

Background— Running an ultramarathon has been shown to have a transient negative effect on right ventricular (RV) and left ventricular (LV) function. Additionally, recent findings suggested that ultraendurance athletes may be more at risk of developing a RV cardiomyopathy. The standard echocardiographic assessment of RV function is problematic; however, the introduction of ultrasonic speckle tracking technology has the potential to yield a comprehensive evaluation of RV longitudinal function, providing new insights into this phenomenon. Thus, the primary aim of this exploratory study was to evaluate comprehensively RV structure and function after a 161-km ultramarathon and establish whether changes in the RV are associated with alterations in LV function. Methods and Results— Myocardial speckle tracking echocardiograms of the RV and LV were obtained before and immediately after a 161-km ultramarathon in 16 healthy adults. Standard echocardiography was used to determine RV size and function and LV eccentricity index. Speckle tracking was used to determine the temporal evaluation of indices of RV and LV function. RV size was significantly increased postrace (RV outflow, 32 to 35 mm, P =0.002; RV inflow, 42 to 45 mm, P =0.027) with an increase in LV eccentricity index (1.03 to 1.13, P =0.006). RV strain (e) was significantly reduced postrace (−27% to −24%, P =0.004), but there was no change in the rates of e. Peak e in all planes of LV motion were reduced postrace (longitudinal, −18.3 to −16.3%, P =0.012; circumferential, −20.2% to −15.7%, P =0.001; radial, 53.4% to 40.3%, P =0.009). Changes in RV size and function correlated with diastolic strain rates in the LV. Conclusions— This exploratory study demonstrates RV dilatation and reduction in function after an ultramarathon. Further research is warranted to elucidate the mechanisms responsible for these findings. It is not clear what clinical impact might result from consecutive bouts of postexercise RV dysfunction.Background— Running an ultramarathon has been shown to have a transient negative effect on right ventricular (RV) and left ventricular (LV) function. Additionally, recent findings suggested that ultraendurance athletes may be more at risk of developing a RV cardiomyopathy. The standard echocardiographic assessment of RV function is problematic; however, the introduction of ultrasonic speckle tracking technology has the potential to yield a comprehensive evaluation of RV longitudinal function, providing new insights into this phenomenon. Thus, the primary aim of this exploratory study was to evaluate comprehensively RV structure and function after a 161-km ultramarathon and establish whether changes in the RV are associated with alterations in LV function. Methods and Results— Myocardial speckle tracking echocardiograms of the RV and LV were obtained before and immediately after a 161-km ultramarathon in 16 healthy adults. Standard echocardiography was used to determine RV size and function and LV eccentricity index. Speckle tracking was used to determine the temporal evaluation of indices of RV and LV function. RV size was significantly increased postrace (RV outflow, 32 to 35 mm, P=0.002; RV inflow, 42 to 45 mm, P=0.027) with an increase in LV eccentricity index (1.03 to 1.13, P=0.006). RV strain (&egr;) was significantly reduced postrace (−27% to −24%, P=0.004), but there was no change in the rates of &egr;. Peak &egr; in all planes of LV motion were reduced postrace (longitudinal, −18.3 to −16.3%, P=0.012; circumferential, −20.2% to −15.7%, P=0.001; radial, 53.4% to 40.3%, P=0.009). Changes in RV size and function correlated with diastolic strain rates in the LV. Conclusions— This exploratory study demonstrates RV dilatation and reduction in function after an ultramarathon. Further research is warranted to elucidate the mechanisms responsible for these findings. It is not clear what clinical impact might result from consecutive bouts of postexercise RV dysfunction.

Mitral annular myocardial velocity assessment of segmental left ventricular diastolic function after prolonged exercise in humans

We assessed segmental and global left ventricular (LV) diastolic function via tissue‐Doppler imaging (TDI) as well as Doppler flow variables before and after a marathon race to extend our knowledge of exercise‐induced changes in cardiac function. Twenty‐nine subjects (age 18–62 year) volunteered to participate and were assessed pre‐ and post‐race. Measurements of longitudinal plane TDI myocardial diastolic velocities at five sites on the mitral annulus included peak early myocardial tissue velocity (E′), peak late (or atrial) myocardial tissue velocity (A′) and the ratio E′/A′. Standard pulsed‐wave Doppler transmitral and pulmonary vein flow indices were also recorded along with measurements of body mass, heart rate, blood pressures and cardiac troponin T (cTnT), a biomarker of myocyte damage. Pre‐ to post‐race changes in LV diastolic function were analysed by repeated measures ANOVA. Delta scores for LV diastolic function were correlated with each other and alterations in indices of LV loading. Diastolic longitudinal segmental and mean TDI data were altered post‐race such that the mean E′/A′ ratio was significantly depressed (1.51 ± 0.34 to 1.16 ± 0.35, P < 0.05). Changes in segmental and global TDI data were not related to an elevated post‐race HR, a decreased post‐race pre‐load or an elevated cTnT. The pulsed wave Doppler ratio of peak early transmitral flow velocity (E)/peak late (or atrial) flow velocity (A) was also significantly reduced post‐race (1.75 ± 0.46 to 1.05 ± 0.30, P < 0.05); however, it was significantly correlated with post‐race changes in heart rate. The lack of change in E/E′ from pre‐ to post‐race (3.4 ± 0.8 and 3.3 ± 0.7, respectively) suggests that the depression in diastolic function is likely to be due to altered relaxation of the left ventricle; however, the exact aetiology of this change remains to be determined.

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.

Exercise-Induced Cardiac Fatigue—A Review of the Echocardiographic Literature

There is growing evidence to support the suggestion that prolonged strenuous exercise has a negative impact on left and right ventricular function during recovery. The main body of evidence covers a 20‐year time window with many studies using transthoracic echocardiography to quantify cardiac function. Although studies have addressed different exercise modes and durations most work has been “field” based. During this time period echocardiographic instrumentation and techniques have evolved significantly and their application in the assessment of prolonged exercise has developed in tandem. The primary objective of this article is to provide reflective insight into the phenomenon of “exercise induced cardiac fatigue” by critically evaluating available literature in different competitive field studies or lab‐based settings. We achieve this objective by introducing the empirical evidence in relation to echocardiographic modalities employed in developmental order including standard 2D, Doppler, tissue Doppler derived myocardial velocity and strain and myocardial speckle tracking echocardiography and by looking at different modes and duration of exercise. The insights provided by data based on each technique are critically reviewed, contradictory findings are explored and the potential for further work is identified. Furthermore the clinical implications and proposed mechanisms of “exercise‐induced cardiac fatigue” are also explored. (Echocardiography 2010;27:1130‐1140)

Left ventricular wall segment motion after ultra-endurance exercise in humans assessed by myocardial speckle tracking

AIMS Assessment of the left ventricular responses to prolonged exercise has been limited by technology available to assess cardiac tissue movement. Recently developed strain and strain rate imaging provide the unique opportunity to assess tissue deformation in all planes of motion. METHODS AND RESULTS Nineteen runners (mean+/-SD age; 41+/-9 years) were assessed prior to and within 60 min (34+/-10 min) of race finish (Comrades Marathon, 89 km). Standard echocardiography assessed ejection fraction and the ratio of early to atrial (E/A) peak transmitral blood flow velocities. Myocardial speckle tracking determined segmental strain as well as systolic and diastolic strain rates in radial, circumferential, and longitudinal planes. Cardiac troponin T (cTnT) assessed cardiomyocyte insult. Ejection fraction (71+/-5 to 64+/-6%) and E/A (1.47+/-0.35 to 1.25+/-0.30) were reduced (P<0.05). Peak strain and peak systolic and diastolic strain rates were altered post-race in circumferential (e.g. peak strain reduced from 21.3+/-2.4 to 17.3+/-3.2%, P<0.05) and radial planes. Some individual heterogeneity was observed between segments and planes of motion. A post-race elevation in cTnT (range 0.013-0.272 microg/L) in 5/12 runners did not differentiate changes in LV function. CONCLUSION Completion of the Comrades Marathon resulted in a depression in ejection fraction, E/A, as well as radial and circumferential strain and strain rates. Group data, however, masked some heterogeneity in cardiac function.

Physiological Right Ventricular Adaptation in Elite Athletes of African and Afro-Caribbean Origin

Background— Regular, intensive exercise results in physiological biventricular cardiac adaptation. Ethnicity is an established determinant of left ventricular remodeling; black athletes (BAs) exhibit more profound LV hypertrophy than white athletes (WAs). Right ventricular (RV) remodeling has not been characterized in BAs, although the issue is pertinent because BAs commonly exhibit ECG anomalies that resemble arrhythmogenic RV cardiomyopathy. Methods and Results— Between 2006 and 2012, 300 consecutive BAs (n=243 males) from 25 sporting disciplines were evaluated by use of ECG and echocardiography. Results were compared with 375 WAs and 153 sedentary control subjects (n=69 blacks). There were no ethnic differences between RV parameters in control subjects. Both BAs and WAs exhibited greater RV dimensions than control subjects. RV dimensions were marginally smaller in BAs than in WAs (proximal outflow tract, 30.9±5.5 versus 32.8±5.3 mm, P<0.001; longitudinal dimension, 86.6±9.5 versus 89.8±9.6 mm, P<0.001), although only 2.3% of variation was attributable to ethnicity. RV enlargement compatible with diagnostic criteria for arrhythmogenic RV cardiomyopathy was frequently observed (proximal outflow tract ≥32 mm; 45.0% of BAs, 58.5% of WAs). Anterior T-wave inversion was present in 14.3% of BAs versus 3.7% of WAs (P<0.001). Marked RV enlargement with concomitant anterior T-wave inversion was observed in 3.0% of BAs versus 0.3% of WAs (P=0.005). Further investigation did not diagnose arrhythmogenic RV cardiomyopathy in any athlete. Conclusions— Physiological RV enlargement is commonly observed in both black and white athletes. The impact of ethnicity is minimal, which obviates the need for race-specific RV reference values. However, in the context of frequent ECG repolarization anomalies in BAs, the potential for erroneous diagnosis of arrhythmogenic RV cardiomyopathy is considerably greater in this ethnic group.

Novel application of flow propagation velocity and ischaemia‐modified albumin in analysis of postexercise cardiac function in man

The present study employed novel echocardiographic tools and cardiac markers to obtain a greater understanding of the aetiology and time course of altered cardiac function and cardiac damage following prolonged exercise and, in particular, the possible role of transient ischaemia within these phenomena. Fourteen runners in the 2004 London Marathon were assessed pre‐, immediately post‐, 1 h post‐ and 24 h postcompletion of the race. Left ventricular function was examined echocardiographically using 2‐D, M‐mode, tissue Doppler imaging and flow propagation velocity (Vp). Venous blood samples were analysed for N‐terminal pro‐B‐type natriuretic peptide (proBNP), cardiac troponin T (cTnT) and ischaemia‐modified albumin (IMA). Left ventricular (LV) diastolic filling was altered on completion of the race, as indicated by significant decreases in mean early to late diastolic myocardial wave (E′:A′) ratio and Vp (from 1.82 ± 0.9 to 1.32 ± 0.32, and from 67.5 ± 9.3 to 60.2 ± 8.2 cm s−1, respectively, P < 0.05), accompanied by an increase in proBNP (from 21.6 ± 11 to 47.08 ± 19.5 pg l−1, P < 0.05). The observed reduction in LV diastolic filling following completion of a marathon, unrelated to changes in heart rate or loading parameters, indicates an intrinsically mediated change in diastolic filling. Exercise‐induced elevations in cTnT in nine individuals (range, 0.023–0.37 μg l−1) were indicative of minor cardiac damage. A significant reduction in IMA was observed after the marathon (from 63.68 ± 9.83 to 44.94 ± 16.13 Um l−1, P < 0.05), unrelated to the alterations in cardiac function, proBNP or cTnT. The absence of an elevation in IMA suggests that exercise‐induced myocardial ischaemia did not occur and therefore could not explain the changes in cardiac function or biomarkers. Future studies in this area should investigate alternative diagnostic tools for the detection of transient ischaemia, and other potential mechanisms, in order to extend the understanding of this phenomenon.