Methods

The Grand Prix of Bern is 1 of the most popular 10-mile races in Switzerland, with >25,000 participants. Nonelite marathon and nonmarathon runners were recruited by an open invitation letter published on the events homepage. We included women and men athletes ≥30 years old. We excluded subjects with hypertension (blood pressure >140/90 mm Hg) and a history of cardiovascular disease except episodes of palpitations or nonsustained arrhythmias. All athletes applied by electronic mail. Study participants were randomly selected and stratified into 3 groups according to former marathon participations: control group (physically active nonmarathon runners), group 1 (1 marathon to 5 marathons), and group 2 (≥6 marathons). Group thresholds were determined after subject selection to ensure equal group sizes. All examinations were performed ≥36 hours after the last strenuous training. A comprehensive questionnaire was used to ascertain personal and sports histories. Lifetime training hours were calculated using the formula: average endurance and strength training hours per week multiplied by 52 multiplied by training years. Assessment included electrocardiography, transthoracic echocardiography, 24-hour Holter monitoring, and cardiopulmonary exercise testing on a treadmill. One experienced cardiologist (M.W.) performed all echocardiographic examinations and was blinded to athletes’ performance and marathon participation status. Intraobserver variability was tested with re-evaluation of 60 randomly selected files on another day. All athletes provided written informed consent and the protocol was approved by the local ethics committee.

Standard transthoracic echocardiography was performed on a Phillips iE33 System (S5-1 2.5-MHz transducer; Phillips Healthcare, Zurich, Switzerland). RA and RV areas were measured in a monoplane in the apical 4-chamber view. RA volume was estimated by the Simpson rule and indexed for body surface area. Left atrial (LA) and left ventricular (LV) volumes were calculated using the biplane method of discs (modified Simpson rule) in the apical 4- and 2-chamber views and indexed for body surface area. Cavity enlargement was defined as RA area >18 cm ² , RV area >25 cm ² , LA volume index >29 ml/m ² , and LV volume index >75 ml/m ² . LV hypertrophy was defined as a LV myocardial mass index >95 g/m ² in women and >115 g/m ² in men. RV systolic function was assessed by fractional area change of RV end-diastolic and end-systolic areas. In addition, tricuspid annular plane systolic excursion, tissue Doppler-derived tricuspid annular basal free RV wall velocity, and myocardial performance index were calculated. LV systolic function was expressed as ejection fraction and derived from LV end-diastolic and end-systolic volumes. RV and LV diastolic functions were assessed by pulse-wave, Doppler, and tissue Doppler in the apical 4-chamber view. Peak early filling and late diastolic filling velocities, peak early filling/late diastolic filling velocity ratio, peak lateral tricuspid velocity, and peak septal mitral annular velocity were recorded. Systolic pulmonary artery pressure was calculated from the sum of peak RV–RA gradient and RA pressure, which were estimated from the inferior vena cava size and colabsibility.

Spiro-ergometric testing was performed on a treadmill. We used a ramp protocol starting at 7.2 km/hour, with speed increasing 0.2 km/hour every 20 seconds until exhaustion. Respiratory parameters were measured continuously in an open spirometric system (CS 200, Schiller-Reomed AG, Dietikon, Switzerland) and registered as averaged values over 30 seconds. Aerobic and anaerobic thresholds were determined according to current recommendations.

Ambulatory electrocardiography was performed over 24 hours and athletes were allowed to exercise at low intensity for 1 hour during recording. Three-channel electrocardiograms were recorded with a Lifecard CF digital recorder (Spacelabs Healthcare, Nuremberg, Germany) and manually analyzed and interpreted using Pathfinder software (Del Mar Reynolds Medical Inc, Irvine, California). Arrhythmias and premature atrial and ventricular contractions were classified according to onset and morphologic QRS interval.

Data were analyzed with SPSS 17.0 Windows (SPSS, Inc., Chicago, Illinois). Normality of quantitative variables was verified with the Kolmogorov–Smirnov test. Categorical data were tested with chi-square test. The 3 groups were compared by analysis of variance or Kruskal–Wallis test, as appropriate. In addition, analysis of covariance was used for adjustment for age, gender, and lifetime training hours. Multiple linear regression analysis was performed to analyze the impact of age, gender, marathon participations, and lifetime training hours on cardiac dimensions and parameters of systolic and diastolic functions. For correlations of atrial and ventricular cavity sizes, Pearson correlation coefficient was calculated. Intraobserver variability was tested with 2 independent measurements of RA volume and RV end-diastolic area and expressed as mean difference, percentage, and intraclass correlation coefficient. A p value <0.05 was considered to indicate statistical significance.

Results

In total 873 athletes (381 women and 492 men) applied for participation, and 68 women and 70 men athletes were randomly selected. Sixteen runners were excluded (9 could not participate in the race because of muscular problems, 1 had mitral valve prolapse, 3 had undiagnosed arterial hypertension with diastolic dysfunction, and 3 did not undergo the examinations). Thus, 122 runners were entered into the final analysis. Mean age was 42 ± 7 years, and marathon runners in group 2 were significantly older than those in group 1 and the control group. Although not significant, there was a trend toward more women runners in groups 1 and 2. The number of former marathons was associated with a lower body mass index and heart rate at rest, more lifetime training hours, and a better 10-mile race time. Blood pressure and average strength training hours did not differ among groups. Four male athletes (3.3% of study participants, 6.6% of men) presented a history of documented paroxysmal atrial fibrillation (AF) and all were marathon runners ( Table 1 ).

Marathon runners showed larger RA and LA volume indexes compared to nonmarathon runners. In group 2, 59.5% and 73.8% of athletes exceeded upper normal limits of RA and LA dimensions, respectively. RV area and LV volume index showed no differences among groups ( Figure 1 ). We found significant correlations of RV end-diastolic area with RA area and of LV volume index with LA volume index ( Figure 2 ). LV myocardial mass increased only in group 2 and concentric LV hypertrophy was significantly more common in marathon runners. RV systolic and diastolic functions were normal in all athletes and showed no significant differences between groups. The same was true for LV systolic and diastolic functions except for peak late septal mitral annular velocity, which was significantly lower in marathon runners ( Table 2 ).

Impact of marathon running on right atrial volume index, right ventricular end-diastolic area, left atrial volume index, and left ventricular volume index in men (triangles) and women (circles) . Mean values are presented (horizontal bars) .

Correlations between right atrial area and right ventricular end-diastolic area and between left atrial volume index and left ventricular volume index. Upper normal limits are presented (dotted lines) .

In multiple linear regression models, marathon participations were an independent predictor of RA area and LA volume index. RV dimensions and RV systolic and diastolic functions were associated only with gender. LV volume index was associated with age, gender, and lifetime training hours, whereas LV systolic function correlated with gender and LV diastolic function inversely with age ( Table 3 ).

Table 3

Independent predictors of atrial and ventricular dimensions and function

	Beta Coefficient	Beta SE	Standardized Beta	p Value
Right atrial area (R 2 = 0.429)
Gender ⁎	4.252	0.518	0.586	<0.001
Marathon participations	1.244	0.371	0.270	0.001
Lifetime training hours	0.000	0.000	0.178	0.023
Right ventricular end-diastolic area (R 2 = 0.376)
Gender ⁎	4.305	0.550	0.599	<0.001
Right ventricular fractional area change (R 2 = 0.171)
Gender ⁎	−0.061	0.014	−0.386	<0.001
Right ventricular myocardial performance index (R 2 = 0.094)
Gender ⁎	−0.042	0.015	−0.272	0.006
Right ventricular early tricuspid annular tissue Doppler velocity (R 2 = 0.218)
Gender ⁎	2.279	0.469	0.415	<0.001
Left atrial volume index (R 2 = 0.347)
Lifetime training hours	0.001	0.000	0.367	<0.001
Marathon participations	2.948	0.726	0.348	<0.001
Age	−0.170	0.071	−0.187	0.018
Left ventricular volume index (R 2 = 0.222)
Age	−0.437	0.106	−0.353	<0.01
Gender ⁎	4.330	1.512	0.238	0.005
Lifetime training hours	0.000	0.000	0.205	0.025
Left ventricular ejection fraction (R 2 = 0.136)
Gender ⁎	−3.610	0.986	−0.321	<0.001
Left ventricular early mitral annular tissue Doppler velocity (R 2 = 0.320)
Age	−0.113	0.017	−0.550	<0.001

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