There is disagreement regarding the actual contribution of systolic and diastolic elements of left ventricular function to the enhancement of cardiovascular athletic performance during exercise(2,12,29). In fact, several methodological problems complicate the evaluation of cardiovascular functional parameters during exercise, due both to different techniques employed in such evaluation(exercise testing, exercise echocardiography, exercise radionuclide angiography, ergospirometric effort) (1,20,32) and to different experimental conditions such as different body position during exercise testing (upright vs supine or semisupine)(23,30). The aim of this study was to assess the behavior of systolic and diastolic left ventricular function with echocardiography and Doppler techniques, simultaneously with ergospirometric evaluation, during maximal semisupine exercise in a group of competitive runners as compared with sedentary controls.
Ten elite males competitive long-distance runners in full training (group A) (mean age 28.5 ± 6.2 yr) and 10 matched sedentary males as a control group (group B) were studied. All studied subjects were free of known cardiac diseases and took no cardiac medications. All subjects were informed of experimental nature of the study and provided written informed consent. The demographic features of these groups are reported in Table 1.
Conventional Doppler-Echocardiography (Basal Evaluation)
M-mode, two-dimensional echocardiograms and Doppler analysis were performed in all subjects by means of a commercially available equipment (Hewlett Packard Sonos 1000, with 2.5- and 3.5- MHz probes). During the basal echocardiographic examination all subjects were in semisupine decubitus, in the same position in which subjects were studied during exercise.
The following hemodynamic parameters were measured from M-mode echocardiography:
- end-diastolic diameter index, by end diastolic diameter corrected by BSA(EDDi);
- end-diastolic septal (STh) and posterior wall thickness (PWTh) in mm;
- left ventricular mass index (g·m-2), ASE formula(LVMi)(26).
The following parameters were derived from two-dimensional echo in four-chamber view:
- end-diastolic (EDV) and end-systolic left ventricular volume (ESV), by using area × length formula;
- ejection fraction, by the formula (EDV-ESV)/EDV;
- mid-diastolic transverse diameter of mitral annulus (mD in cm) was measured from the second or third video frame after the initial maximal opening motion of the anterior leaflet. Measurements were taken from the inner edge of the lateral bright corner of the annulus to the inner edge of the medial corner just below the insertion of the mitral leaflets, in an apical four-chamber view;
- cross-sectional area of the mitral annulus (π × r2), where r is half of the annular diameter (m-CSA in cm2).
Pulsed Doppler echocardiography was performed with the same transducer. The sample volume was positioned just below the level of the insertion of the mitral valve leaflets; the following parameters were evaluated:
- peak E (peak transmitral flow velocity in early diastole);
- peak A (peak transmitral flow velocity in late diastole);
- E/A ratio;
- isovolumic relaxation time (IRT) (by placing the sample volume half way between mitral and aortic valves, this period could be measured as the interval between the end of the aortic and the beginning of the mitral flow velocity profile);
- time-velocity integral of mitral inflow (mTVI);
- stroke volume (SV, in ml), calculated as: SV=mTVI × mCSA; since Doppler evaluation of SV can be obtained through mitral flow examination(18);
- cardiac output (CO), calculated as: SV × HR(l·min-1).
Heart rate (HR) was assessed simultaneously with the echocardiography examination by ECG. Arterial blood pressure was measured by sphygmomanometer(in mm Hg): systolic arterial pressure (SAP); diastolic arterial pressure(DAP); and MAP by the formula DAP+1/3 (SAP - DAP).
All subjects had excellent acoustic windows both at rest and during exercise. At least 1 wk in advance of the test, a maximal semisupine bicycle exercise stress test was performed simultaneously with spirometric evaluation, at an initial workload of 25 W and with 25 W increments every 1 min, to evaluate the maximal ergometric and aerobic capacity. All subjects subsequently underwent a simultaneous echocardiographic, electrocardiographic, and ergospirometric evaluation at rest (level 1); at 50% of their known maximal aerobic capacity (in full aerobic period) (level 2); at peak of exercise (during anaerobic period) (level 3); and during the recovery time, 4 min after the end of exercise (level 4). Heart rate, blood pressure, systolic and diastolic left ventricular functional, and ergospirometric parameters were evaluated.
Exercise Doppler Echocardiography
In apical four-chamber view, images were recorded on video throughout the study period for subsequent off-line analysis. Regarding the critical sampling at peak of exercise, the probe was placed in apical four-chamber view a few minutes before muscular exhaustion and the real-time evaluation of the selected parameters was carried out from 0 to 30 sec after the end of exercise. EDV, ESV, peak E, peak A, relative E/A ratio, and isovolumic relaxation time were measured during exercise. Pulsed Doppler recordings of diastolic transmitral flow velocity profiles were obtained with the sample volume located at the tips of the mitral leaflets (in the apical four-chamber view). Doppler sample volume size was set at its lower limit (approximately 5 mm). Gain settings were optimized to enhance endocardial edge and spectral displays. Care was taken to align the sample volume as perpendicular as possible to the mitral annulus, to record appropriately flow velocity. Video recordings of two-dimensional and Doppler echocardiograms were analyzed off-line by an experienced echocardiographer, using the Hewlett-Packard software of analysis. To assess reproducibility of the Doppler echocardiographic measurements, were analyzed on two separate occasions for intraobserver variability, as well as by a investigator blinded for interobserver variability. Both inter- and intraobserver variability were between 2% and 6%; correlations between measured parameters ranged from 0.91 to 0.97 for interobserver and from 0.94 to 0.98 for intraobserver variability. Measurements were derived by averaging at least five consecutive cardiac cycles. Isovolumic relaxation time was corrected for heart rate by Bazett's formula (time/√R - R interval).
Simultaneous with the echocardiographic examination, all athletes performed an ergospirometric study with an MMC HORIZON SYSTEM 4400tc (Sensormedics); the following parameters were evaluated at the same sampling moments of the echocardiographic examination: oxygen uptake (˙VO2);(˙VO2·kg-1); CO2 production(˙VCO2).
Changes in cardiac and spirometric parameters either within stages of exercise on groups, were compared by two-way analysis of variance (stages of protocol and groups) with repeated measurements on one factor (stages of protocol) and a simultaneous testing of hypotheses using Bonferroni inequality. A probability < 0.05 was considered significant. All data are reported as mean ± standard deviation.
Athletes and controls were males, matched as to age (28.5 ± 6.2 vs 30.4 ± 3.3 yr; P = NS), height, weight, and relative body surface (Table 1).
Resting heart rate was lower in athletes than in controls (58.5 ± 8.7 vs 72.8 ± 7.6 min-1; P < 0.001), while blood pressure was comparable (Table 2). Resting end diastolic indexed diameter of the left ventricle was greater in athletes than in sedentary subjects (2.88 ± 0.2 vs 2.45 ± 0.2 cm; P< 0.01) (Table 1). Septum thickness in diastole was significantly greater in athletes than in sedentary (1.17 ± 0.1 vs 1.03± 0.06 cm; P < 0.002) (Table 1). Left ventricular mass index was higher in athletes than in controls (151.8 ± 24.1 g·m-2 vs 109.4 ± 16.3; P < 0.0001)(Table 1). Left ventricular end diastolic volume, at rest, was greater in athletes than in controls (138.7 ± 13.5 vs 98.5 ± 17.3 ml; P < 0.001); end systolic volume was greater in athletes than in sedentary subjects (53.8 ± 6.3 vs 32.6 ± 7.1 ml;P < 0.01) (Table 2). Left ventricular ejection fraction, at rest, was comparable in both groups(Table 2). Stroke volume was significantly greater in athletes than in controls (82.3 ± 12.7 vs 67.8 ± 10.3 ml,P < 0.005) (Table 2). In rest conditions peak A of Doppler mitral flow was significantly lower in athletes than in controls(0.40 ± 0.1 vs B: 0.56 ± 0.1, m·s-1; P< 0.006) while isovolumic relaxation time was higher in athletes in comparison with controls (12.0 ± 1.5 vs B: 9.8 ± 1.9,P < 0.01.) (Table 3). At rest no significant differences were found for spirometric parameters, between the two groups.
At the end of exercise, work load was higher in athletes than in controls(312.5 ± 31.2 vs 196.8 ± 31.1 W; P < 0.001)(Table 2). Systolic blood pressure in athletes increased at cessation by 58% in comparison with resting value (P < 0.005), while in sedentary controls the increase was smaller (48%, P < 0.01); the comparison between groups showed a SAP value at the end of exercise higher in athletes than in controls (P < 0.001)(Table 2). Heart rate increased more in athletes versus controls, compared with resting values (+187%, P < 0.001 vs+127%, P < 0.01), but reached the same values in absolute terms(Table 2); these values referred to HR at sampling time and were lower than real peak exercise HR (group A: 174.5 ± 12.3 vs group B: 177.3 ± 18.5, NS), because delayed of few seconds (0-30 s). Left ventricular end-diastolic volume was significantly higher in athletes than in controls at all levels of exercise (Fig. 1); a slight though not significant increase in EDV was observed in athletes at the end of exercise versus rest (Table 2), while in the control group the EDV did not show significant variations. Left ventricular end-systolic volume in athletes decreased significantly at the end of exercise in comparison with resting values (P < 0.05); in controls the ESV decrease was not significant. When comparing the two groups, ESV was greater in athletes at all levels of sampling (P < 0.01). Left ventricular ejection fraction showed a significant incremental behavior in athletes, comparing peak of exercise with resting values (P < 0.01). At cessation, a slight but insignificant increase in EF was also observed in the control group as compared with rest. The comparison between groups showed a significantly higher EF in athletes both at cessation and during recovery time (P < 0.05) (Table 2).
Mitral valve diameter and relative cross-sectional area did not show significant variations during either exercise or recovery. Mitral flow derived stroke volume was significantly higher in athletes than in controls at all levels of exercise (Table 2). A significantly increase was observed (+26%, P < 0.01) only in athletes, when SV at the end of exercise was compared with resting value. At peak, cardiac output increased by 240% in athletes, while in controls the increase was of 135%; the comparison between groups showed a CO significantly higher in athletes than in controls(P < 0.008) (Fig. 2).
Regarding diastolic function at the end of exercise, a significant increase in peak E over resting values (P < 0.01) was observed in both groups; however, the absolute value of peak E was greater in athletes than in controls (Fig. 3). As to the sampling of peak A at the end of exercise, the E and A waves overlapped because of high heart rates. The IRTc did not exhibit significant differences during exercise in the two groups(Table 3).
The ˙VO2·kg-1 and ˙VCO2 increased in both groups during exercise. ˙VO2max·kg-1 and˙VCO2 at peak of exercise were higher in athletes than in sedentary subjects (P < 0.0001) (Table 4).
In both groups there was a parallel decrease in heart rate and mean blood pressure at the end of exercise. During recovery, SV increased significantly in athletes group, as compared with peak exercise values (P < 0.01), due to an increment of venous return as documented by increased EDV; the same parameter did not show a similar increase in the control group(Table 2).
The response to exercise of cardiovascular system is quite complex and results from the interaction of changes in heart rate, contractility, preload, and afterload (5). Still carefully debated is the extent of the increase in stroke volume during exercise and how the left ventricle increases its output during maximal exercise. In humans many studies have demonstrated that exercise-related stroke volume increases are accompanied by concomitant reduction in ESV (11,13). On the other hand, conflicting results have been reported regarding the changes of end-diastolic volume during exercise (15), probably due to different techniques employed in examining left ventricular function(27). Furthermore, substantial differences were described for the effect of body posture during exercise, in particular between upright and supine or semisupine position. Regarding the latter, cardiac output rises as a function of stroke volume and ejection fraction, while left ventricular end-diastolic pressure remains relatively constant. In the upright position, instead, the infrathoracic pooling of blood below the thorax reduces end-diastolic pressure and volume, at rest and both increase during exercise, with a parallel in SV and EF (19) changes. In this study the semisupine position obligated optimization of the echocardiographic examination.
The group of athletes were able to perform a greater work load with higher exercise duration, in comparison with the control group. This finding is consistent with literature data and results from a direct effect of training on cardiovascular system and peripheral exercised muscles.
Left Ventricular Systolic Function in the Athlete's Heart
Intense training of elite endurance runners induces a number of cardiovascular adjustments, which integrated by complex neurophysiological modifications and athletes' genetic characteristics(6,7) are the major determinants of athletic fitness and power. In fact, ˙VO2max is directly related to cardiac output and to arterial-venous oxygen saturation, and aerobic power reflects the pulmonary capacity of oxygen transport, muscular oxygen extraction, and an activated aerobic metabolism (16). The effect of training on cardiovascular structures could be summarized as a“physiological” left ventricular hypertrophy that counterbalances the dilation of left ventricular chamber due to the higher blood volume in athletes compared with sedentary subjects. Stroke volume can be modified by training; on the other hand, the blood volume increase that occurs in athletes has a direct effect on the cardiac preload and on left ventricular chamber dilatation. Although left ventricular systolic function, at rest, was superimposable to controls (25), the athlete's heart was further characterized by a low heart rate under resting conditions caused by sympathetic nervous system modulation induced by training.
At the end of exercise both groups reached about 85% of the maximum age-predicted heart rate, although neither group achieved the maximal heart rate due to the unusual position of exercise and to of the nose clip used for a correct evaluation of expiratory gas exchange. A potential concern regarding our study is the reliability of two-dimensional left ventricular volumes and performance measurements during exercise (Fig. 1); since two-dimensional left ventricular volumes underestimate with those derived from invasive evaluation; although ejection fraction obtained by two-dimensional echocardiography and cineangiography are nearly equivalent. To adjust for this problem, Doppler-derived values of stroke volume were used, given the higher precision of SV estimate by this method (10). We found an higher left ventricular ejection fraction in athletes, at all levels of semisupine exercise and a significant increase from rest was observed both at the end of exercise and during recovery (control subjects showed a similar behavior, although to a lesser extent). This greater increase in EF could be explained by the greater change of both in end diastolic and in end systolic volume in athletes. In the latter EDV increased slightly at exercise levels 2 and 3 (Fig. 1), but the ESV did not change significantly at any level of exercise. At level 3, heart rate and mean arterial pressure were comparable in both groups; the workload reached by athletes was significantly higher than that of controls at both levels 2 and 3 of exercise. A greater SV in athletes than in controls at all exercise levels and its significant increase at cessation are the determinants of the higher CO observed in athletes (Fig. 2). The absolute value of CO in our study was underestimated, both for methodological implications relative to Doppler SV estimate and for the rapid reduction of HR during the Doppler sampling after stopping exercise due to intense parasympathetic activity during recovery period.
In athletes we observed a progressive increase in stroke volume during exercise. Therefore, we have hypothesized an interaction of different mechanisms able to explain this hemodynamic effect. The increase in heart rate, per se, contributes to augmentation of cardiac contractility through operation of the interval-strength relation (4) adrenergic stimulation (10) and the operation of Frank-Starling mechanism, through an increase in preload consequent to augmentation of venous return during exercise due to pumping action of trained skeletal muscles and to a lower intrathoracic pressure during exercise at inspiration (24) These mechanisms may explain the higher CO in athletes at every exercise level, despite the progressive reduction in diastolic filling related to HR increase.
On the other hand, in sedentary controls the cardiac output level achieved at cessation was maintained only through heart rate and adrenergic stimulation mechanisms, without Frank-Starling law activation.
During recovery, in both groups, a further, significant EDV increase was observed, higher in athletes than in controls; this finding may be due to the increased venous return from peripheral muscles accompanied by the decrease of heart rate, which results in greater ventricular filling. A direct consequence of this phenomenon is the activation of Frank-Starling mechanism, especially in athletes, which slightly improves ejection fraction and stroke volume in both groups. The other parameters progressively return to basal values.
Left Ventricular Diastolic Function in the Athlete's Heart
Diastolic function at rest has been extensively studied, whereas few investigators evaluated diastolic filling during exercise in men. Pulsed Doppler echocardiography of mitral flow has been shown to be a reliable method for assessing left ventricular diastolic filling in healthy and pathological states. This method has been validated in comparison with both cineangiographic and radionuclide techniques. Our data in rest condition are comparable with other studies, confirming the better compliance in trained subjects (9,31). During exercise, in previous studies a linear correlation was found between peak E and HR(3,21); the most important factors affecting the behavior of peak E are heart rate, mean arterial pressure cardiac output, and˙VO2max (8).
Recent reports studied left ventricular hypertrophy in athletes, analyzing myocardial structure through ultrasonic tissue characterization with integrated backscatter. These studies showed that left ventricular hypertrophy of the athletic heart is physiological. In fact, the integrated backscatter signals of left ventricular walls in athletes were comparable with those of sedentary controls (17). Left ventricular diastolic function in endurance athletes observed at rest appeared comparable to that of sedentary controls. Such data are in agreement with those described in the present study. The most relevant findings, at rest, were a significantly lower peak A in athletes compared with age-matched controls, which may explain the significantly higher E/A ratio in athletes; and a higher mitral acceleration time and isovolumic relaxation time, when compared with controls(14,22).
During exercise at 50% of aerobic capacity, both groups were comparable as to diastolic parameters, except for the significantly higher IRTc in athletes. At cessation, only a higher peak E was observed in athletes as compared with controls (Fig. 3). These data confirm that left ventricular mass of athletes does not affect the diastolic function at rest. Furthermore, the significant increase in Doppler-derived early transmitral flow velocity in athletes and the superimposable behavior of other diastolic parameters during exercise in both groups suggest an enhancement that occurs in athletes in the active phase of diastole for the better use of preload reserve. The left ventricular diastolic compliance observed in athletes permits a good left ventricular filling, essentially in the early diastolic phase, that allows an excellent left ventricular systolic performance. Studies in rats have shown that exercise training decreases the contraction duration, due to a shortened relaxation time, improves the rate of decline of the left ventricular pressure (maximum -dP/dt), decreases the time constant of relaxation (τ), increases calcium uptake by the sarcoplasmic reticulum, and increases fatty acid oxidation and cytochrome C oxidase levels(28). It is uncertain what mechanisms actually underlie the improved diastolic function during exercise in trained subjects.
Limitations of the Study
We did not use invasive methods to measure systolic and diastolic function, as these were deemed inappropriate in a healthy asymptomatic population. Furthermore, in the absence of invasive data, in particular of the intraventricular pressure-time relationship, we are uncertain as to whether the improvement in diastolic function during exercise is due to intense training or to the variations of loading conditions of the left ventricle induced by exercise. Another limitation was the fact that exercise was performed in the supine position, which is known to result in a different sequence of hemodynamic responses as compared with exercise in the upright position.
This methodological approach allows a complex analysis of the cardiovascular response to exercise; in fact, it is possible to examine both systolic and diastolic left ventricular function as well as to estimate, noninvasively, the behavior of stroke volume, cardiac output, and maximal oxygen consumption, which are the main determinants of exercise capacity. All the cardiovascular adjustments induced by training in runners, both in systolic and diastolic phase, are related to an increase in cardiac output and in maximal oxygen consumption, which results in enhanced sporting performances.
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Keywords:©1996The American College of Sports Medicine
EXERCISE DOPPLER ECHOCARDIOGRAPHY; ERGOSPIROMETRIC EXERCISE TEST