ABSTRACT
Background
Athlete’s heart, characterized by cardiac chambers adaptations to exercise has some diagnostic overlaps with dilated cardiomyopathy (DCM). In the setting of differential diagnosis, myocardial work indexes (MWI), afterload-independent tool, could be helpful to identify early subclinical alterations. The aim of our study was to assess the utility of MWI in athletes with mildly reduced left ventricular ejection fraction (LVEF).
Methods
We enrolled 306 Olympic athletes (55.5% males) practicing endurance and mixed disciplines, mean age 26.3 ± 4.3 years old, who underwent cardio-pulmonary exercise test (CPET) and transthoracic echocardiogram. Athletes were divided in those with lower (<55%) and normal LVEF (≥55%). Strain rate and MWI were performed and the following parameters collected: global longitudinal strain, global myocardial work index (GWI), constructive myocardial work (CMW), wasted myocardial work (WMW) and global cardiac work efficiency (GWE).
Results
Twenty-seven athletes had LVEF<55% (mean 51.5% ± 2.6%). Athletes with EF < 55% presented larger LVEDVi (79.1 ± 15.7 vs. 73.2 ± 13.8 mm/m2, P =.035), LV mass ( P =.049) and LAVi ( P =.016). No differences were found in GWI (1,757.9 ± 242 vs 1,839.8 ± 255.6 mmHg%, P =.112), GCW (2,121.6 ± 269.3 vs. 2,209.3 ± 281 mmHg%, P =.124), GWW (95.2 ± 40.7 vs. 87.1 ± 47.4 mmHg%, P =.394) or GWE (95.2 ± 1.7 vs. 95.7 ± 2%, P =.181). At CPET, in those with EF < 55%, higher Watts (340.0 ± 83.7 vs. 291.6 ± 84.8, P =.004), VO 2 mL/min/Kg (51.0 ± 13.5 vs. 46.0 ± 10.1, P =.020) and O2 pulse (23.5 ± 4.6 vs. 21 ± 5.3, P =.020) were found.
Conclusions
MWI could be used as additive tool to characterize the physiologic nature of mildly reduced EF of endurance athletes, presenting with better functional parameters but preserved MWI values. MWI may be helpful in differential diagnosis of athlete’s heart from DCM.
A small but significant number of highly-trained and apparently healthy athletes exhibits an enlarged left ventricular (LV) cavity exceeding normal values, which in some cases may be associated with a borderline or mildly reduced ejection fraction (EF) (LVEF, <55% but >45%), representing a grey area that overlaps between an athlete’s heart and an early stage of dilated cardiomyopathy (DCM). This issue has been frequently reported in endurance athletes, especially elite and professional cyclists, triathletes and long-distance runners.
The clinical approach to addressing this challenging differential diagnosis has mainly focused on the response of the dilated/hypokinetic LV to exercise, with exercise-echocardiography being proposed as the most effective test for distinguishing between these 2 conditions. , Millar et al. developed a comprehensive diagnostic protocol, where exercise-echocardiography proved to have the highest diagnostic capacity. However, in clinical practice, exercise-echocardiography is not always feasible, even in young athletes, due to imaging limitations, particularly when the heart rate approaches maximum levels, as needed to effectively test LV contractility. For this reason, clinicians are keen to find additional tools to assist in this challenging diagnostic scenario.
Myocardial work indexes (MWI) are new echocardiographic parameters based on pressure strain loop, which combine myocardial deformation imaging using 2 Dimensional Speckle Tracking Echocardiography (2D-STE) and noninvasive afterload determination using brachial cuff blood pressure measurement. MWI have proven to be relative afterload-independent and related to myocardial deformation and contractile function. , In contrast to LV EF, MWI have been shown to be helpful in distinguishing physiological adaption (eg, eccentric LV remodeling) from pathological changes (eg, DCM). ,
In fact, even in early stages, individuals with heart failure with preserved ejection fraction (HFpEF) exhibit lower MWI such as resting global work efficiency (GWE) values and higher resting global wasted work (GWW) values. Those with reduced GWE display lower exercise capacity, increased pulmonary congestion, and attenuated LV contractile reserve during exercise.
Aim of our study was to evaluate the utility of MWI to characterize endurance elite athletes presenting with lower EF and distinguishing them from those with normal EF values, in order to timely identify individuals with subclinical pathologic conditions.
Material and methods
The Institute of Sport Medicine and Science in Rome, of the Italian National Olympic Committee, is responsible for conducting medical evaluation of athletes selected for major events including the Olympic Games, World Championships, and Mediterranean Games. The research methods used in this study were reviewed and approved by the Review Board of the Institute of Medicine and Sports Science. All athletes participating in the study were thoroughly informed about the evaluation process and gave their informed consent in accordance with Italian law and institutional guidelines. The clinical data collected from the study participants are stored in a dedicated institutional database. The procedures followed here align with The Code of Ethics of the World Medical Association (Declaration of Helsinki).
For this study, we enrolled 306 elite athletes who were evaluated in preparation for the 2024 Paris Olympic Games. Athletes underwent a thorough, multidisciplinary preparticipation screening, which included a complete physical exam, extensive blood tests, resting electrocardiography (ECG), transthoracic echocardiography (TTE), and a cardiopulmonary exercise test (CPET). Female athletes were evaluated in the same period of their menses.
We focused on athletes competing in disciplines with a significant training-induced volume overload (ie, mixed and endurance athletes) as these athletes usually develop the most marked cardiac remodeling. Athletes in skill-based or power sports were not included in the study. Additionally, those undergoing chronic medication therapy and individuals diagnosed with cardiac abnormalities were also excluded.
Athletes participated in the following disciplines :
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Endurance: cycling, rowing, canoeing, triathlon, long-distance running, long-distance swimming (over 800 meters), cross-country skiing, pentathlon, biathlon, Nordic combined, and long-distance ice skating.
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Mixed disciplines: soccer, fencing, volleyball, basketball, tennis, water polo and beach volleyball.
Anthropometric measurements were obtained, with body composition and percentage of body fat determined utilizing Bioelectric Impedance Analysis (BIA101 Quantum, Akern, Pisa, Italy) employing a constant sinusoidal current at a frequency of 50 kHz and an intensity of 400 µA. Height and weight were recorded for each subject, and body mass index (BMI) was computed as weight (in kilograms) divided by height (in meters) squared. Body surface area (BSA) was calculated using the Mosteller formula.
A standard 12-lead ECG was conducted with the subject in a supine position, and interpretation was performed in accordance with international criteria for ECG interpretation in athletes. As advised, blood pressure was assessed via noninvasive brachial cuff measurement while in a supine position at rest, concurrently with the acquisition of apical views by TTE, prior to the execution of CPET. Athletes were considered to have lower EF if a value under 55% was calculated, according to current literature on elite athletes.
Transthoracic echocardiogram
The echocardiographic assessment was performed on subjects in a resting state, positioned in the left lateral decubitus orientation. The echocardiographic examinations were conducted by a single physician (GP) with expertise in sports-related cardiac imaging and athlete’s heart physiology. All echocardiographic measurements were executed by an experienced sports cardiologist (GDG).
Ultrasound data acquisition was performed utilizing a GE Vivid E9 ultrasound system equipped with a 4Vc phased array probe (GE Healthcare Vingmed Ultrasound AS, Horten, Norway). Subsequent postprocessing analyses were undertaken utilizing the EchoPac software (Version 203, GE Healthcare Vingmed Ultrasound AS, Horten, Norway). A comprehensive 2D echocardiographic study was carried out, wherein cardiac images were captured in various cross-sectional planes employing established transducer positions. According to prevailing recommendations, measurements of left ventricle (LV) end-diastolic diameter (LVEDD), left ventricle end-systolic diameter (LVESD), interventricular septal (IVS) thickness and posterior wall thickness (PWT) were taken in the parasternal short-axis section of the LV. The relative wall thickness (RWT) was calculated using the ratio of (IVS + PWT) to LVEDD. LV mass (LVM) was derived using the Devereux formula, with measurements indexed to body surface area (BSA). An LVM index > 115 g/m 2 for males and > 95 g/m2 for females was indicative of LV hypertrophy.
LV systolic function was assessed based on LV ejection fraction (EF), derived from LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) computed through LV biplane planimetry employing the modified Simpson’s rule in both the apical 2- and 4-chamber views. Diastolic function was evaluated using both pulsed-wave Doppler (PW) and tissue Doppler imaging (TDI), involving the measurement of maximum blood flow velocities (Vmax) of E- and A-wave, E/A-ratio, as well as myocardial Vmax of e′ and a′ at the basal septal and lateral tricuspid annulus, along with the septal E/e′-ratio. Left atrial (LA) volume was determined using the biplane method. The right ventricular (RV) chamber was evaluated in accordance with established guidelines. Right atrial (RA) area and RV function parameters were assessed in the RV-focused apical 4-chamber view. This involved tracing the endocardial contour to measure end-diastolic and systolic areas, from which fractional area change (FAC) was calculated and expressed as a percentage. Tricuspid annular plane systolic excursion (TAPSE) was measured as an indicator of RV longitudinal systolic function. Peak tricuspid regurgitant velocity and the systolic trans-tricuspid gradient were determined using continuous wave Doppler on the tricuspid regurgitation jet. Pulmonary artery systolic pressure (PASP) was calculated by adding the systolic trans-tricuspid gradient to the value of right atrial pressure (RAP). The latter was estimated using the inferior vena cava (IVC) dimension, inspiratory collapsibility, and RV function. In all athletes, 3 consecutive cardiac cycles were assessed in accordance with current literature.
Intra-observer and inter-observer variability for main LV parameters such as LVEDD, IVS, and LVEDV was assessed in a sample of 100 athletes, selecting randomly 1 every 8 athletes from our database, independent of sex and sporting discipline. Two investigators (GDG and AP) blinded measured the same exam. Both investigators repeated the analysis 3 days later, blinded to the previous measurements. Interclass correlation coefficients (ICC) for LVEDD identification were 0.94 for intra-observer and 0.93 for inter-observer agreement; for IVS, ICC was 0.96 for intra-observer and 0.94 for inter-observer agreement and for LVEDV, ICC was 0.92 for intra-observer and 0.90 for inter-observer agreement.
Two-dimensional speckle-tracking echocardiography (2DSTE)
Quantification of 2D strain was performed using commercially available software (EchoPAC TM workstation Centricity TM Cardio Workflow, version 6.0 SP6, GE Healthcare, EEUU). According to current recommendations, 2D gray-scale images were obtained from the apical 2- chamber, 4-chamber and long-axis views at a frame rate of 50-80 frames/second. By manually clicking on the mitral annulus and apex of 3 sections at the end-systolic frame, the region of interest between the endocardium and epicardium was automatically defined using 2D-STE. ,, The operator assessed the tracking quality and the region of interest (ROI) was adjusted by correcting the endocardial border or width if deemed necessary. Aortic valve closure was identified using the automated function from the apical long-axis view. Peak LV global longitudinal strain (GLS) was then performed using echocardiography software that divided the myocardium into 6 segments in each view, creating graphs of shortening over the cardiac cycle. A bull’s-eye plot was created of peak LV GLS for each myocardial segment. Therefore, the GLS was calculated from the average value of the 3 views, including 17 segments of the myocardium and expressed as bull’s-eye. If the software did not correctly identify the LV wall movement without assigning a strain value to the LV segment (poor tracking), the operator repeated the process, readjusted the endocardial tracing, or changed software parameters, such as ROI width and smoothing until a better score was achieved.
Myocardial work
Global myocardial work index was calculated using a specific software (EchoPAC ver. 202, GE Vingmed Ultrasound, Norway) with a combination of LV strain and a noninvasively estimated LV pressure with noninvasive blood pressure measurement to attain a pressure-strain loop (PSL) of the LV, as previously described by Russel et al. Arterial blood pressure was measured immediately before the echocardiographic examination, following a 5-minute period of rest in a seated position. According to recent guidelines, arterial blood pressure was measured for 3 times (1-2 min apart) and the average of the last 2 reading was done
The software constructed a noninvasive LV-pressure curve, which was adjusted according to the duration of isovolumic and ejection phases defined by valvular-timing events. The area within the curve was an index of Myocardial Work (MW). An additional set of indices was used, as already described in previous studies , :
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Global myocardial work index (GWI): is the total work within the area of the LV PSL between mitral valve closure and mitral valve opening.
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Global Constructive myocardial Work (GCW): representing positive work, was the work performed by the myocardium that was productive to LV ejection fraction, a combination of the shortening of the LV during systole and the expansion of the LV during isovolumic relaxation. In particular GCW was calculated with the following formula: GCW=∫Systole(PositiveStrain×LVPressure)+∫IsovolumicRelaxation(NegativeStrain×LVPressure)
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Global Wasted myocardial Work (GWW): representing the energy loss, the work that was unproductive to LV ejection fraction, a combination of lengthening during systole and shortening during isovolumic relaxation. In particular GWW was calculated with the following formula:GWW=∫Systole(NegativeStrain×LVPressure)+∫IsovolumicRelaxation(PositiveStrain×LVPressure)
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Global cardiac work efficiency (GWE): reflects the efficiency of mechanical energy to perform work in the whole cardiac cycle; it is the ratio of constructive work to total work; expressed as CMW/(CMW + WMW) × 100% per segment and GWE as an average of all segmental values.
Intra-observer and inter-observer variability were assessed also for MWI, including GWI, GCW, GWW, and GWE. ICC for GWI identification were 0.92 for intra-observer and 0.91 for inter-observer agreement; for GCW, ICC was 0.95 for intra-observer and 0.92 for inter-observer agreement; for GWW, ICC was 0.92 for intra-observer and 0.91 for inter-observer agreement and for GWE ICC was 0.95 for intra-observer and 0.21 for inter-observer Discrepancies between observers were resolved by consensus.
Cardio-pulmonary exercise test (CPET)
We conducted CPET on a cycle ergometer (COSMED). The protocol included a 1-minute rest, a 2-minute warm-up without any load, and subsequent increments of 15-20-25-30 Watt with a ramp protocol, depending on gender and sports discipline, until exhaustion. Continuous ECG monitoring and recording (Quark T12x, COSMED) took place during the warm-up, exercise, and subsequent recovery period, which lasted for 5 minutes. Additionally, we utilized a breath-by-breath metabolimeter (Quark CPET; COSMED) to measure oxygen consumption and carbon dioxide production throughout the entire cardiopulmonary assessment.
We recorded the following parameters at peak:
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VO2 in absolute (mL/min) and relative (mL/min/kg) values.
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Power (expressed in Watts).
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Heart rate (HR), bp.
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Respiratory Quotient (RQ).
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Oxygen Pulse (VO 2 /HR).
When reaching both the first (lactate) threshold and second (respiratory compensation) threshold, measurements were conducted for:
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Power (expressed in Watts).
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VO 2 (mL/min).
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The slope of work efficiency (VO 2 /watts).
Statistical analysis
Categorical variables were expressed as frequencies and percentages (in parenthesis) and were compared using Fisher’s exact test or Chi-square test, as appropriate. Normality criteria were checked for any continuous variable, which was presented as mean and standard deviation (SD) and compared using the Student t-test for independent data if normally distributed. The comparative analysis between the different group was performed using the Dunn test and Pairwise comparison method. All pairwise tests were considered significant if P <.05. Statistical analysis was performed with STATA Statistics for Windows (SE, version 17) software.
Results
We enrolled 306 elite athletes (170, 55.5% males) practicing mixed disciplines ( n = 161, 52.6%) and endurance ( n = 145, 47.4%), mostly engaged in cycling ( n = 32, 10.5%), rowing ( n = 41, 13.4%), volleyball ( n = 41, 13.4%) and water polo ( n = 37, 12.1%) and marathon running ( n = 23, 7.5%).
Mean age was 26.3 ± 4.3 years; body weight 76.8 ± 14.8 kg, and BMI 23 ± 3.1 kg/m 2. Athletes were engaged in a very intensive training schedule, with 24 ± 7.1 hours per week of training at the time of evaluation.
Twenty-seven (8.8%) athletes had EF lower than 55%, ranging 47% to 55%. They were prevalently males (22, 81.5%), with higher male prevalence compared to other with normal values (53%, P =.004), Table 1 . Athletes with EF < 55% were primarily engaged in cycling ( n = 8), rowing ( n = 5), marathon runners ( n = 3), with very few in volleyball ( n = 5), fencing ( n = 2), canoeing ( n = 1), basketball ( n = 1), water polo ( n = 1) and tennis ( n = 1) with a prevalence ranging from 25% in cyclists and 15% in rowers to lower prevalence in those practicing group sports (4.3% basketball, 2.7% waterpolo).
Table 1
Comparison of clinical and anthropometric parameters between athletes with reduced and normal ejection fraction.
| N, (%) | Lower EF | Preserved EF | P |
|---|---|---|---|
| 27 (8.8) | 279 (91.2) | ||
| Age, years | 27.5 ± 3.5 | 26.2 ± 4.4 | .155 |
| Male, n (%) | 22 (81.5) | 148 (53) | .004 |
| Weight, kg | 77.1 ± 11.4 | 76.3 ± 14.9 | .787 |
| BMI, kg/m 2 | 22.8 ± 2.3 | 23 ± 3.2 | .806 |
| BSA | 1.99 ±.18 | 1.96 ± 0.25 | .531 |
| Afro-Caribbean, n (%) | 2 (7.4) | 15 (5.4) | .660 |
| Training hours\week | 24.8 ± 7.4 | 23.9 ± 7.2 | .555 |
Abbreviations: BMI, body mass index; BSA, body surface area.
In those with EF < 55%, there was, therefore, an higher prevalence of athletes practicing endurance disciplines ( n = 17\27, 63%, compared to those practicing mixed sports, n = 10/27, 37%, with values close to statistical significance, P =.056).
Athletes with lower vs. those with preserved EF did not show significance differences in terms of age, anthropometric parameters and global training volume (24.8 ± 7.4 hours per week vs. 23.9 ± 7.2, P =.555).
In Table 2 are listed main echocardiographic differences between athletes with lower EF vs. those with preserved one. Athletes with lower EF had larger LV volumes indexed (both diastolic and systolic, respectively, P <.0001), higher LVMi ( P =.049) and lower LV GLS ( P =.0003) compared to those with preserved EF. Moreover, lower E wave ( P =.031), lower E/A ratio ( P =.028) and lower E/E’ ( P =.021) were observed in athletes with reduced EF. Significant differences were also noted for the other chambers, including a larger LA (both diameter and volume, respectively P =.002 and P =.016), RA area ( P =.047) and RV area (both diastolic and systolic, respectively P =.042 and P =.024).
Table 2
Comparison of echocardiographic parameters between athletes with reduced and normal ejection fraction.
| Lower EF | Preserved EF | P | ||
|---|---|---|---|---|
| N, (%) | 27 (8.8) | 279 (91.2) | ||
| LV | LVEDDi, mm/m 2 | 28.6 ± 3.1 | 28.2 ± 3 | .490 |
| LVESDi, mm/m 2 | 19.3 ± 4.3 | 17.5 ± 2.4 | .0003 | |
| IVS, mm | 9.5 ± 0.8 | 9.2 ± 1.2 | .206 | |
| PWT, mm | 8.8 ± 0.8 | 8.6 ± 1.2 | .392 | |
| LVEDVi, mL/m 2 | 79.1 ± 15.7 | 73.2 ± 13.8 | .035 | |
| LVESVi, mL/m 2 | 37.3 ± 8.3 | 27.1 ± 6.4 | <.0001 | |
| LVMi, gr/m 2 | 100.9 ± 17.8 | 93.4 ± 19.3 | .049 | |
| EF, % | 51.5 ± 2.6 | 62.9 ± 5.2 | <.0001 | |
| GLS, % | −18.7 ± 2 | −20.4 ± 2.2 | .0003 | |
| GWI, mmHg% | 1757.9 ± 242 | 1839.8 ± 255.6 | .112 | |
| GCW, mmHg% | 2121.6 ± 269.3 | 2209.3 ± 281 | .124 | |
| GWW, mmHg% | 95.2 ± 40.7 | 87.1 ± 47.4 | .394 | |
| GWE, % | 95.2 ± 1.7 | 95.7 ± 2 | .181 | |
| E wave, cm/sec | 71.6 ± 15.4 | 78.8 ± 16.7 | .031 | |
| A wave, cm/sec | 42.6 ± 11.5 | 40.5 ± 9.5 | .296 | |
| E\A | 1.8 ± 0.5 | 2.1 ± 0.7 | .028 | |
| E’, m/sec | 12.3 ± 1.9 | 12 ± 2.6 | .583 | |
| A’, m/sec | 6.7 ± 1.6 | 6.4 ± 1.7 | .493 | |
| S’, m/sec | 7.3 ± 1.4 | 7.7 ± 1.9 | .367 | |
| E/E’ | 6 ± 1.3 | 6.8 ± 1.8 | .021 | |
| LA | TD, mm | 41.3 ± 5.7 | 38.2 ± 5 | .002 |
| LD, mm | 39 ± 3.9 | 36.6 ± 5 | .013 | |
| LAVi, mL/m 2 | 28.6 ± 9.2 | 25.1 ± 7.1 | .016 | |
| S_CD, % | −26.6 ± 5.5 | −28.9 ± 7.2 | .115 | |
| S_CT, % | −9.5 ± 4.4 | −10.4 ± 4.5 | .324 | |
| S_R, % | 37.9 ± 7.1 | 39.5 ± 8.5 | .221 | |
| RV | GLS, % | −19 ± 2.7 | −19.4 ± 5.2 | .741 |
| E’, m/sec | 14.8 ± 3.6 | 14.6 ± 3.1 | .791 | |
| A’, m/sec | 10 ± 2.7 | 8.9 ± 2.6 | .062 | |
| S’, m/sec | 12.4 ± 2.3 | 12.9 ± 2.6 | .383 | |
| EDAi, mm 3/m 2 | 12.6 ± 3.1 | 11.5 ± 2.7 | .042 | |
| ESAi, mm 3/m 2 | 7.1 ± 1.9 | 6.3 ± 1.8 | .024 | |
| FAC, % | 43 ± 8.7 | 45.1 ± 7.5 | .196 | |
| EDDi, mm/m 2 | 20.5 ± 2.9 | 20.6 ± 3 | .881 | |
| TAPSE, mm | 27.8 ± 4.8 | 26.6 ± 4 | .140 | |
| IVC, mm | 21.5 ± 4.5 | 17.5 ± 3.7 | <.0001 | |
| RA | TD, mm | 42.6 ± 5.9 | 40.8 ± 6.2 | .153 |
| RAAi, mm 2/m 2 | 9.5 ± 2.3 | 8.7 ± 1.9 | .047 | |
| S_CD, % | −24.9 ± 6.1 | −26.9 ± 8.6 | .238 | |
| S_CT, % | −8.3 ± 4.3 | −9.7 ± 4.9 | .156 | |
| S_R, % | 33.3 ± 7.7 | 36.7 ± 9.9 | .085 | |
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