Background
Echocardiography has been used to determine ventricular function, segmental wall motion abnormality, and pulmonary artery pressure before and after peak exercise. No prior study has investigated systolic and diastolic function using echocardiography at various phases of exercise in children. The aim of this study was to determine the fractional shortening (FS), systolic-to-diastolic (S/D) ratio, heart rate–corrected velocity of circumferential fiber shortening (VCFc), circumferential wall stress (WS), ratio of mitral passive inflow to active inflow (E/A), ratio of passive inflow by pulsed-wave to tissue Doppler (E/E′), and right ventricular–to–right atrial pressure gradient from tricuspid valve regurgitation jet velocity (RVP) and time duration at various phases of exercise in children.
Methods
In an 8-month period (December 2007 to July 2008), 100 healthy children were evaluated, and 97 participants aged 8 to 17 years who performed complete cardiopulmonary exercise stress tests using supine cycle ergometry were prospectively enrolled. The participants consisted of 48 female and 49 male subjects with various body sizes, levels of exercise experience, and physical capacities. The cardiopulmonary exercise stress test consisted of baseline pulmonary function testing, continuous gas analysis and monitoring of blood pressure and heart rate responses, electrocardiographic recordings, and oxygen saturation measurement among participants who pedaled against a ramp protocol based on body weight. All participants exercised to exhaustion. Echocardiography was performed during exercise at baseline, at a heart rate of 130 beats/min, at a heart rate of 160 beats/min, at 5 min after exercise, and at 10 min after exercise. FS, S/D ratio, VCFc, WS, E/A, E′, E/E′, and RVP at these five phases were compared in all subjects.
Results
All echocardiographic parameters differed at baseline from 160 beats/min ( P < .0001) except E/E′, which remained at 5.4 to 5.8. Specifically, FS (from 37% to 46%), S/D ratio, VCFc (from 1.1 to 1.6), WS (from 200 to 258 g/cm 2 ), E′ (from 0.2 to 0.3), and RVP (from 18 to 35 mm Hg) increased from baseline to 160 beats/min and then subsequently decreased to at or near baseline, while tricuspid valve regurgitation duration decreased (from 370 to 178 msec).
Conclusions
Normal values for systolic and diastolic echocardiographic measurements of function are now available. FS, VCFc, WS, and RVP increase with exercise and then return to near baseline levels. The E/E′ ratio is unaltered with exercise in normal subjects.
Exercise echocardiography has been used to quantify ventricular function, segmental wall motion abnormalities, and pulmonary artery pressure before and at peak exercise. These measurements have also been obtained at various phases of exercise. In the pediatric patient population, however, there is a concern that echocardiographic data may not represent the true peak measurement because of heart rate recovery. No prior study has investigated the parameters of systolic and diastolic function during physical exertion at different phases of exercise. In this initial, prospective investigation, we endeavored to determine the feasibility of obtaining two-dimensional and spectral Doppler imaging during exercise. Additionally, we sought to determine functional changes during different phases of exercise in normal, healthy children. This study provides echocardiographic function measurements for children during exercise.
Methods
Patient Population
Healthy volunteers aged 8 to 17 years were enrolled prospectively from December 2007 to July 2008 at the Lucile Packard Children’s Hospital Heart Center at Stanford University as a part of an internal grant. The following data were collected from each subject: date of birth, gender, body surface area (Haycock formula), height, weight, baseline blood pressure, and an exercise activity questionnaire. Inclusion criteria were a structurally normal heart and normal sinus rhythm, established at baseline echocardiography. Exclusion criteria were body mass index > 35 kg/m 2 , developmental delay, moderate to severe pulmonary limitations assessed by pulmonary function tests, short leg length, submaximal effort during exercise test, inability to perform exercise on a cycle ergometer, drop in systolic blood pressure during exercise, pathologic ST-segment changes during exercise, and any significant childhood disease. This study was approved by the Stanford University Institutional Review Board; informed consent and assent were obtained.
Exercise Protocol
All 97 participants performed baseline pulmonary function testing to assess forced vital capacity, forced expiratory volume in 1 sec, forced expiratory flow at 25% to 75% of forced vital capacity, and maximum voluntary ventilation. A complete cardiopulmonary exercise stress test was also performed on a supine cycle ergometer (Medical Positioning, Minneapolis, MN) that used a Medical Graphics Ultima Cardio2 system to analyze breath-by-breath metabolic measures, assessed continuous electrocardiographic recordings and oxygen saturation, and collected blood pressure measurements every 2 min. Participants pedaled at a rate of 50 to 60 rpm and performed against a ramp protocol based on body weight (0.25 × body weight [kg]), reported exercise experience, and physical abilities and tolerance. All participants began with pulmonary function testing before the cardiopulmonary exercise test. The cardiopulmonary exercise test consisted of an initial warm-up in which participants pedaled for 2 min at 0 W before pedaling against increased workloads. Participants exercised to exhaustion followed by a 5-min cool-down period. Before the onset of the cardiopulmonary exercise test, the participants had baseline heart rates < 100 beats/min and respiratory exchange ratios (RERs) < 1.00. They exercised to exhaustion and were considered to have met maximal exercise parameters by reaching an RER > 1.00 and a target heart rate ≥ 160 beats/min. The RER is the ratio of the net output of carbon dioxide to the simultaneous net uptake of oxygen and an indicator of substrate utilization. During exercise, this is directly related to lactic acid accumulation in muscle and is used to objectively quantify effort. The following parameters were measured at each protocol point: blood pressure, heart rate, and ventilatory equivalents. There were five protocol points: (1) baseline before exercise (rest), (2) a heart rate of 130 beats/min during exercise, (3) a heart rate of 160 beats/min during exercise, (4) 5 min after exercise in recovery, and (5) 10 min after exercise in recovery. Notably, all echocardiographic measurements at heart rates of 130 and 160 beats/min were obtained while cycling ( Figure 1 ).
Echocardiographic Data
Echocardiographic studies were performed using a Phillips iE33 (Philips Medical Systems, Bothell, WA). The syngo Dynamics workstation (Siemens Medical Solutions USA, Inc., Mountain View, CA) was used to perform offline analysis of M-mode and Doppler-derived velocities. All echocardiographic imaging was performed at the five protocol points using standard imaging techniques. A parasternal short-axis image was obtained at the mitral valve leaflets and at the papillary muscle level to calculate a systolic-to-diastolic ratio (S/D) and fractional shortening (FS) using M-mode techniques. The systolic and diastolic time intervals were measured by examining the mitral valve opening and closing, respectively, using M-mode ( Figure 2 ). The time spent in systole was divided by the time spent in diastole to obtain the S/D ratio. From the standard apical view, the following echocardiographic data were obtained: (1) tricuspid valve regurgitation (TR) jet velocity and TR duration (TRTD) using continuous-wave Doppler imaging closely aligned with flow, (2) mitral valve pulsed-wave Doppler inflow to measure the E/A ratio, (3) mitral valve annular velocity using Doppler tissue imaging at the lateral wall to determine E′ and derive the ratio of mitral passive inflow (E) to E′, and (4) left ventricular ejection time and left ventricular length to calculate the heart rate–corrected velocity of circumferential fiber shortening (VCFc) and circumferential wall stress (WS).
At each protocol point, the following echocardiographic measurements were obtained: FS, S/D, E/A, E/E′, TR jet velocity, and TRTD. To remove heart rate effects on the TRTD comparison, corrected TRTD was calculated as TRTD/√RR, using the heart rate at rest and a heart rate of 160 beats/min. The right ventricular–to–right atrial pressure gradient was calculated using the modified Bernoulli equation. A biplane measurement of ejection fraction was also attempted at each protocol point. All measurements were made by one observer (D.Y.O.). A subset of 10 patients was analyzed by a second, independent reader (R.P.) for four of the same echocardiographic measurements (FS, S/D, E/A, and E/E′) at the five different states of exercise to determine interobserver variability. The second reader was blinded to the recorded clip and frame number of the first reader.
Statistical Analysis
All values for FS, S/D, VCFc, WS, E/A, E/E′, TR pressure gradient, TRTD, and corrected TRTD are expressed as mean ± SD. Our primary interest was to compare observations at rest and at heart rate of 160 beats/min. The distribution of the difference for these variables met the assumption of normality, and therefore the paired t test was used to test for statistical significance. A heart rate of 130 beats/min was additionally compared with the heart rate at 5 min in recovery using a paired t test post hoc. This was done to determine if the echocardiographic measurements immediately after peak exercise (as is currently performed in many laboratories) reflects true real-time findings during exercise and can be compared, as loading conditions are dissimilar under these scenarios. Intraclass correlation coefficients were used to establish interobserver variability for the echocardiogram measurements at 160 beats/min, because this protocol point should have the worst agreement. To help control for a pyramiding type 1 error, we applied Bonferroni’s correction to these statistical comparisons and considered P values < .005 (.05/10 = .005) to indicate statistical significance. Statistical calculations were performed using SAS Enterprise Guide version 4.2 (SAS Institute Inc., Cary, NC) and Microsoft Excel (Microsoft Corporation, Redmond, WA).
Results
Patient Population
One hundred patients were enrolled in this study, and 97 met the inclusion criteria. Three subjects were excluded because of submaximal effort during exercise. There were 48 female and 49 male patients. The average age was 12.7 ± 2.4 years ( Table 1 ). The mean weight and body surface area were 47.3 ± 14.4 kg and 1.4 ± 0.3 m 2 , respectively. Only eight of the 97 patients listed no physical activities on the study questionnaire. Forty-two of the 97 subjects listed single organized sports. Twenty-three listed two and 24 listed three or more organized sports.
| Variable | Value |
|---|---|
| Age (y) | 12.7 ± 2.4 (8.1–17.8) |
| Female/male | 48/49 |
| Weight (kg) | 47.3 ± 14.2 (24.0–103.0) |
| Body surface area (m 2 ) | 1.4 ± 0.3 (0.9–2.2) |
Exercise Protocol
All patients were exercised to exhaustion with an average RER of 1.18 ± 0.09 and an average maximum heart rate of 185 ± 10 beats/min. The average maximal oxygen consumption was 93.7 ± 8.6% of predicted. The average time of cycling against a load to maximal oxygen consumption was 14.5 ± 2.6 min, and the average total exercise time was 18.9 ± 3.3 min. The ramp measured 14.2 ± 4.1 W/min, while the maximum load measured 147.8 ± 54.5 W. The heart rate and blood pressure responses were appropriate during the different phases of exercise, with a statistically significant increase from rest to 160 beats/min ( P < .0001; Figure 3 ). The heart rate at 130 beats/min was significantly higher at 5 min, which measured 120 ± 13 beats/min ( P < .0001). Thus, the loading conditions would be different at those two protocol points, and inferences about heart rate recovery and its effects on echocardiographic function data cannot be made. The heart rate at 10 min did not appear to fall back to the measurements at rest. There were no significant ST-segment changes or decreases in blood pressure during the study.
Echocardiographic Data
All systolic and diastolic measurements of function were measured for each gender group ( Table 2 ). The same ventricular function assessment was applied to children at four specified age ranges ( Table 3 ).
| Echocardiographic parameter | Condition | Female patients | Male patients |
|---|---|---|---|
| FS | Rest | 36.4 ± 5.4 | 37.1 ± 5.1 |
| HR 130 beats/min | 44.1 ± 6.0 | 46.1 ± 6.7 | |
| HR 160 beats/min | 45.1 ± 5.9 | 47.6 ± 6.6 | |
| 5 min | 44.0 ± 4.5 | 44.3 ± 5.6 | |
| 10 min | 37.2 ± 4.5 | 38.2 ± 4.8 | |
| S/D | Rest | 0.6 ± 0.2 | 0.5 ± 0.1 |
| HR 130 beats/min | 1.0 ± 0.1 | 0.9 ± 0.2 | |
| HR 160 beats/min | 0.9 ± 0.2 | 0.9 ± 0.2 | |
| 5 min | 0.8 ± 0.1 | 0.8 ± 0.1 | |
| 10 min | 0.8 ± 0.1 | 0.8 ± 0.1 | |
| VCFc | Rest | 1.1 ± 0.2 | 1.2 ± 0.2 |
| HR 130 beats/min | 1.4 ± 0.2 | 1.5 ± 0.3 | |
| HR 160 beats/min | 1.6 ± 0.2 | 1.7 ± 0.3 | |
| 5 min | 1.2 ± 0.1 | 1.3 ± 0.2 | |
| 10 min | 1.0 ± 0.1 | 1.2 ± 0.2 | |
| E/A | Rest | 2.1 ± 0.5 | 2.2 ± 0.5 |
| HR 130 beats/min | 1.3 ± 0.4 | 1.1 ± 0.2 | |
| HR 160 beats/min | 1.1 ± 0.1 | 1.2 ± 0.2 | |
| 5 min | 1.4 ± 0.3 | 1.5 ± 0.3 | |
| 10 min | 1.4 ± 0.3 | 1.6 ± 0.5 | |
| E′ | Rest | 0.2 ± 0.0 | 0.2 ± 0.0 |
| HR 130 beats/min | 0.3 ± 0.0 | 0.2 ± 0.1 | |
| HR 160 beats/min | 0.3 ± 0.1 | 0.3 ± 0.1 | |
| 5 min | 0.2 ± 0.0 | 0.2 ± 0.0 | |
| 10 min | 0.2 ± 0.0 | 0.2 ± 0.0 | |
| E/E′ | Rest | 5.3 ± 1.1 | 5.5 ± 1.1 |
| HR 130 beats/min | 5.7 ± 1.0 | 5.9 ± 1.2 | |
| HR 160 beats/min | 5.4 ± 1.1 | 5.5 ± 1.1 | |
| 5 min | 5.4 ± 1.2 | 5.4 ± 1.4 | |
| 10 min | 5.4 ± 1.3 | 5.2 ± 1.2 | |
| TRPG | Rest | 17.8 ± 3.3 | 18.0 ± 4.8 |
| HR 130 beats/min | 30.9 ± 5.3 | 38.6 ± 8.0 | |
| HR 160 beats/min | 34.0 ± 7.7 | 37.5 ± 4.8 | |
| 5 min | 20.9 ± 4.9 | 22.8 ± 4.6 | |
| 10 min | 18.1 ± 3.4 | 18.7 ± 4.8 | |
| TRTD | Rest | 370.1 ± 32.9 | 369.2 ± 31.0 |
| HR 130 beats/min | 217.2 ± 26.0 | 213.9 ± 34.4 | |
| HR 160 beats/min | 179.7 ± 19.2 | 178.4 ± 32.4 | |
| 5 min | 314.7 ± 47.7 | 302.0 ± 39.1 | |
| 10 min | 347.6 ± 38.2 | 335.9 ± 37.4 |
| Echocardiographic parameter | Condition | Age group (y) | |||
|---|---|---|---|---|---|
| 8–9 ( n = 16) | 10–11 ( n = 27) | 12–13 ( n = 28) | 14–17 ( n = 26) | ||
| FS | Rest | 37.4 ± 6.0 | 38.1 ± 5.1 | 36.3 ± 4.9 | 35.7 ± 5.2 |
| HR 130 beats/min | 45.1 ± 5.3 | 46.4 ± 7.3 | 45.2 ± 6.7 | 44.2 ± 6.2 | |
| HR 160 beats/min | 47.4 ± 4.9 | 47.1 ± 5.0 | 46.7 ± 7.7 | 44.7 ± 6.7 | |
| 5 min | 43.8 ± 5.2 | 44.1 ± 5.6 | 44.0 ± 4.5 | 44.6 ± 5.3 | |
| 10 min | 39.5 ± 3.4 | 36.4 ± 4.5 | 38.0 ± 5.3 | 37.7 ± 4.7 | |
| S/D | Rest | 0.6 ± 0.2 | 0.6 ± 0.1 | 0.5 ± 0.1 | 0.5 ± 0.1 |
| HR 130 beats/min | 1.0 ± 0.2 | 1.0 ± 0.2 | 0.9 ± 0.2 | 0.9 ± 0.1 | |
| HR 160 beats/min | 1.0 ± 0.2 | 0.9 ± 0.2 | 0.9 ± 0.2 | 0.9 ± 0.2 | |
| 5 min | 0.8 ± 0.1 | 0.8 ± 0.1 | 0.8 ± 0.1 | 0.7 ± 0.1 | |
| 10 min | 0.9 ± 0.2 | 0.9 ± 0.1 | 0.8 ± 0.1 | 0.8 ± 0.1 | |
| VCFc | Rest | 1.1 ± 0.2 | 1.2 ± 0.2 | 1.1 ± 0.2 | 1.1 ± 0.2 |
| HR 130 beats/min | 1.5 ± 0.2 | 1.5 ± 0.3 | 1.5 ± 0.3 | 1.4 ± 0.2 | |
| HR 160 beats/min | 1.3 ± 0.3 | 1.2 ± 0.2 | 1.2 ± 0.1 | 1.3 ± 0.2 | |
| 5 min | 1.2 ± 0.3 | 1.1 ± 0.2 | 1.1 ± 0.3 | 1.0 ± 0.2 | |
| 10 min | 1.7 ± 0.2 | 1.7 ± 0.2 | 1.7 ± 0.4 | 1.6 ± 0.2 | |
| E/A | Rest | 2.2 ± 0.6 | 2.0 ± 0.4 | 2.2 ± 0.6 | 2.1 ± 0.5 |
| HR 130 beats/min | 1.1 ± 0.1 | 1.4 ± 0.5 | 1.1 ± 0.1 | 1.2 ± 0.2 | |
| HR 160 beats/min | NA | 1.1 ± 0.2 | 1.2 ± 0.1 | 1.2 ± 0.2 | |
| 5 min | 1.5 ± 0.3 | 1.5 ± 0.4 | 1.4 ± 0.3 | 1.4 ± 0.3 | |
| 10 min | 1.6 ± 0.4 | 1.6 ± 0.5 | 1.5 ± 0.4 | 1.3 ± 0.3 | |
| E′ | Rest | 0.2 ± 0.0 | 0.2 ± 0.0 | 0.2 ± 0.0 | 0.2 ± 0.0 |
| HR 130 beats/min | 0.2 ± 0.0 | 0.2 ± 0.0 | 0.2 ± 0.0 | 0.3 ± 0.1 | |
| HR 160 beats/min | 0.3 ± 0.1 | 0.3 ± 0.0 | 0.3 ± 0.0 | 0.3 ± 0.1 | |
| 5 min | 0.2 ± 0.0 | 0.2 ± 0.0 | 0.2 ± 0.0 | 0.2 ± 0.1 | |
| 10 min | 0.2 ± 0.0 | 0.2 ± 0.0 | 0.2 ± 0.0 | 0.2 ± 0.0 | |
| E/E′ | Rest | 5.7 ± 1.2 | 5.6 ± 1.3 | 5.4 ± 0.9 | 5.1 ± 1.1 |
| HR 130 beats/min | 5.9 ± 0.9 | 5.5 ± 1.3 | 6.1 ± 1.0 | 5.7 ± 1.2 | |
| HR 160 beats/min | 5.6 ± 1.2 | 5.2 ± 1.1 | 5.6 ± 0.9 | 5.3 ± 1.1 | |
| 5 min | 5.4 ± 1.1 | 5.0 ± 1.3 | 5.5 ± 1.3 | 5.7 ± 1.5 | |
| 10 min | 5.5 ± 1.2 | 5.0 ± 1.3 | 5.6 ± 1.3 | 5.2 ± 1.1 | |
| TRPG | Rest | 17.3 ± 2.9 | 17.8 ± 4.6 | 18.2 ± 4.6 | 18.1 ± 4.6 |
| HR 130 beats/min | 32.0 ± 18.2 | 34.9 ± 4.2 | 34.3 ± 6.3 | 35.1 ± 9.5 | |
| HR 160 beats/min | 32.9 ± 7.6 | 38.7 ± 5.9 | 33.9 ± 7.9 | NA | |
| 5 min | 20.7 ± 6.5 | 20.5 ± 5.1 | 23.6 ± 2.9 | 22.4 ± 4.6 | |
| 10 min | 16.3 ± 3.6 | 18.0 ± 4.4 | 21.3 ± 3.0 | 18.2 ± 4.2 | |
| TRTD | Rest | 360.4 ± 31.5 | 363.4 ± 30.5 | 376.7 ± 28.3 | 374.2 ± 35.7 |
| HR 130 beats/min | 224.4 ± 24.6 | 216.7 ± 27.3 | 216.1 ± 42.0 | 208.9 ± 19.1 | |
| HR 160 beats/min | 310.2 ± 43.4 | 313.6 ± 46.8 | 306.8 ± 38.3 | 303.2 ± 48.0 | |
| 5 min | 339.6 ± 36.9 | 349.9 ± 37.7 | 339.4 ± 37.6 | 337.2 ± 40.5 | |
| 10 min | 186.5 ± 24.4 | 171.7 ± 18.8 | 187.4 ± 35.5 | 173.4 ± 19.2 | |
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