Left Ventricular, Left Atrial and Right Ventricular Strain Modifications after Maximal Exercise in Elite Ski-Mountaineering Athletes: A Feasibility Speckle Tracking Study

ld elite ski-mountaineering (Ski-Mo) athletes were evaluated for pronounced echocardiographic physiological remodeling as the primary aim of our feasibility speckle track- ing study. In this context, sports-related cardiac remodeling was analyzed by performing two- dimensional echocardiography, including speckle tracking analysis of the left atrium (LA), right ventricle (RV) and left ventricular (LV) global longitudinal strain (LV-GLS) at rest and post-peak performance.

elite ski-mountaineering (Ski-Mo) athletes were evaluated for pronounced echocardiographic physiological remodeling as the primary aim of our feasibility speckle track- ing study. In this context, sports-related cardiac remodeling was analyzed by performing two- dimensional echocardiography, including speckle tracking analysis of the left atrium (LA), right ventricle (RV) and left ventricular (LV) global longitudinal strain (LV-GLS) at rest and post-peak performance. The feasibility echocardiographic speckle tracking analysis was performed on eleven elite Ski-Mo athletes, which were obtained in 2022 during the annual medical examination. The obtained data of the professional Ski-Mo athletes (11 athletes, age: 18–26 years) were compared for different echocardiographic parameters at rest and post-exercise. Signi cant differences were found for LV-GLS mean (p= 0.0036) and phasic LA conduit strain pattern at rest and post-exercise (p= 0.0033). Furthermore, negative correlation between LV mass and LV-GLS (p= 0.0195, r = 0.69) and LV mass Index and LV-GLS (p= 0.0253, r = 0.66) at rest were elucidated. This descriptive reporting provided, for the rst time, a sport-speci c dynamic remodeling of an entire elite national team of the Ski-Mo athlete's left heart and elucidated differences in the dynamic deformation pattern of the left heart. Keywords: cardiopulmonary exercise testing; echocardiography; strain analysis; ski-mountaineering; training; athlete's physique 1. Introduction Ski mountaineering (Ski-Mo) has been accepted as a new Olympic sport for the 2026 Milan-Cortina Olympics [1]. Ski-Mo has been rated among the most strenuous endurance sports with the highest “hypoxic dose”(i.e., time spent in a hypoxic environ- ment) [2–5], as it demands both maximal endurance performance during the individual races as well as high-intensity bouts during the sprint and vertical races in elite winter sports athletes [2–4,6–9]. Int. J. Environ. Res. Public Health2022,19, 13153.

Int. J. Environ. Res. Public Health2022,19, 13153 2 of 13 In comparison to other winter endurance sports, e.g., Nordic Cross Country skiing or biathlon, Ski-Mo involves long uphill and downhill passages that have highly varying muscular demands. This leads to signi cantly different athletic features in comparison to other professional winter sports athletes [8]. Ski-Mo athletes tend to be smaller and younger than other elite endurance winter sports athletes [6–8]. In this context, signi cant physiological differences in morphological and functional cardiac remodeling could be identi ed for Ski-Mo athletes, especially due to left atrial (LA) remodeling, speckle tracking analysis of the left ventricle (LV), LV ejection fraction (LV-EF) assessment and LV Mass index [6–8]. The term athlete's heart describes adaptions, namely physiological, functional and electro-physiological, caused by variable physiological sport-speci c demands [8]. A conventional morphological and functional echocardiographic assessment might fail to dis- tinguish between an athlete's heart and controls, whereby functional strain rate evaluation provides further information for subclinical abnormalities and risk strati cation [8,10–19]. These relatively new, non-invasive imaging techniques enhance the understanding of an athlete's heart through a comprehensive characterization of anatomical and functional adap- tion, providing novel insights into the assessment of cardio-physiological adaption [20]. Especially the analyzed innovative echocardiographic data on pre- and post-exercise conditions with particular attention to the application of speckle tracking as dynamic functional assessment of cardiac remodeling might provide further insights into the char- acterization of biventricular and LA function in athletes and the impact of sport-speci c cardiocirculatory functional adaption in these athletes [20]. The scienti c evidence on the physiological aspects of competitive Ski-Mo athletes is still sparse. However, so far sport speci c cardiopulmonary remodeling due to structural and functional adaption of the athlete's heart has already been proven [6–8,21–23]. Under resting conditions sport speci c structural remodeling, such as left atrial volume index (LAVI) and LV global longitudinal strain (LV-GLS), could be detected [7,8]. The objective of the present scienti c analysis is to investigate the feasibility of biventricular and LA phasic deformation patterns after maximal exercise, as earlier studies solely focused on strain analysis

already been proven [6–8,21–23]. Under resting conditions sport speci c structural remodeling, such as left atrial volume index (LAVI) and LV global longitudinal strain (LV-GLS), could be detected [7,8]. The objective of the present scienti c analysis is to investigate the feasibility of biventricular and LA phasic deformation patterns after maximal exercise, as earlier studies solely focused on strain analysis at rest. In this context, the aim of this feasibility study is to investigate the correlations between strain pattern at rest and their dynamic changes post-exercise to enhance our understanding of an athlete's heart. This comprehensive characterization of biventricular and LA functions might provide novel insights into the physiological adaption of an athlete's heart, especially under environmental conditions, such as speci c altitude training conditions [20,24]. Previous research revealed a complex sport-speci c interaction between physiological response and altitude training, whereby hypoxia and training stress are combined [25]. Alterations of the autonomous regulation of the nervous system and subsequent modi cations of the heart rate variability (HRV) have been studied before, differently depending on the training intensity at altitude [25–28]. These peculiarities might be promising to provide further interesting data to distinguish sport-speci c cardiac remodeling in these elite world winter sports professionals, who often perform their sports in altitude, from balanced cardiomyopathies in the future [7,8,20]. 2. Materials and Methods The local ethics committee of the University of Bayreuth approved the study protocol (O1305/1-GB). The study was conducted in conformity with the declaration of Helsinki and Good Clinical Practice [29]. Before any study-related activities, our participating athletes were informed about the study protocol, and athletes were asked to give their written informed consent. 2.1. Study Population Eleven young elite Ski-Mo professionals, all active members of the German National Team, participating in World championships and the World Cup season, were examined and evaluated in the preseason preparation time in summer during the season 2022. No

Int. J. Environ. Res. Public Health2022,19, 13153 3 of 13 participating athlete had to be excluded from the study due to post-COVID-19 infection syndromes. All participants were evaluated for anthropometric data, 12 lead electrocar- diogram (ECG) and two-dimensional transthoracic echocardiography, including strain analysis at rest and post-exercise. The obtained data of the athletes (n= 11; malen= 8, femalen= 3) were compared for different echocardiographic parameters at rest and post- exercise. All participating athletes did not have any medical history, and their sports-related history revealed no potential risk factors for sudden cardiac death in all athletes and within their families. All participating Ski-Mo athletes were winter sports professionals with a total amount of 20–30 training hours per week during high-volume training times and 5–10 training hours during low-volume training times. During low-volume training times, the athletes focus on continuous endurance training, such as running and cycling, as well as functional strength training and individual training to improve muscle disbalances [6]. An additional sample size estimation was not conducted since the includedn= 11 represents the entire cohort of the German National Team competing at World Cup and World Championship levels. 2.2. Echocardiographic Examination An echocardiographic functional and morphological assessment at rest and post- exercise using a commercially available echocardiographic system Phillips EPIQ 7 device with an X5-1 Matrix-array transducer (Phillips Healthcare, Eindhoven, The Netherlands), following a standard protocol, was performed [30]. In addition, heart rate and blood pres- sure were measured. Two-dimensional echocardiographic analyses were performed at rest following the general recommendations [8,30–32]. The systolic LV-EF was calculated using biplane Simpson rule, based on the apical two-chamber—as well as apical four-chamber view. Two-dimensional linear dimensions and LAVI were evaluated for both ventricles and both atria manually according to the recommendations [30–33]. An estimation of the RV systolic function at rest using the TAPSE (Tricuspide annular plane systolic excursion) was obtained in the apical four-chamber view. The LV Mass index and the relative wall thickness (RWT) of the LV were calculated using the formula recommended by the current guidelines [34]. We measured the pulse-wave Doppler in the apical four-chamber view referring to the

estimation of the RV systolic function at rest using the TAPSE (Tricuspide annular plane systolic excursion) was obtained in the apical four-chamber view. The LV Mass index and the relative wall thickness (RWT) of the LV were calculated using the formula recommended by the current guidelines [34]. We measured the pulse-wave Doppler in the apical four-chamber view referring to the peak early lling (E wave) and late diastolic lling (A wave) velocities to assess the LV diastolic function. Additionally, tissue Doppler imaging of the lateral mitral anulus in the apical four-chamber view was performed (peak early velocity E 0 ) [30,31]. Furthermore, speckle tracking analysis of the athlete's heart was recorded at rest as well as three minutes post maximal treadmill cardiopulmonary exercise testing (CPET) as post-exercise assessment, focusing on LV, RV and LA. In this context, we obtained the LV-GLS pattern, RV free wall longitudinal deformation (RV FW long.Def.), RV four chamber longitudinal deformation (RV 4C long.Def.) as well as phasic LA strain analysis by two-dimensional strain analysis in the apical views. The detailed phasic LA strain analysis was performed according to the recent European Association of Cardiovascular Imaging (EACVI) recommendations, including LA reservoir strain (LASr), LA conduit strain (LAScd) and LA contraction strain (LASct) assessment [35]. The LA strain assessment was not limited because no Ski-Mo athlete presented atrial brillation. Each of the participating Ski-Mo athletes was evaluated for the prevalence of left and right heart valve regurgitation as part of the standard echocardiographic assessment [8,30,36]. 2.3. Statistical Analyses Data were analyzed with Graph Pad Prism 8.2.1(279) (Graph Pad Software; San Diego, CA, USA). All data were tested for normal distribution via Shapiro–Wilk test. Data were tested for differences with pairedt-tests, with statistical signi cance being accepted at p 0.05. All data are presented as mean SD. Pearson correlations were conducted for anatomical echocardiographic parameters as independent parameter with GLS, RV deformation pattern and LA reservoir, LA conduit and LA contractile at resting conditions as well as post-exercise in our participating elite Ski-Mo athletes. Due to the relatively small

p 0.05. All data are presented as mean SD. Pearson correlations were conducted for anatomical echocardiographic parameters as independent parameter with GLS, RV deformation pattern and LA reservoir, LA conduit and LA contractile at resting conditions as well as post-exercise in our participating elite Ski-Mo athletes. Due to the relatively small

Int. J. Environ. Res. Public Health2022,19, 13153 4 of 13 number of participating elite winter sports athletes, who were enrolled as the uniqueness of this reporting, we are not able to draw reliable conclusions by uni- and multivariate regression analyses, but we might point out interesting trends in the cohort of enrolled world elite winter sports professionals. 3. Results 3.1. Baseline Athletes' Characteristics and Echocardiographic Assessment at Rest The baseline characteristics and anthropometric data of the participating male and female Ski-Mo athletes are presented in Table. The body surface areas were calculated with the Du Bois method. In the two-dimensional echocardiographic assessment, all participating Ski-Mo ath- letes showed a low–normal to normal systolic LV-EF at rest estimated by the biplane Simpson method and did not show any relevant pathological regurgitation of the right and left heart valves. Only mild regurgitation at the tricuspid and mitral valves was re- vealed. There was no relevant systolic pulmonary artery pressure evaluated by tricuspid peak systolic velocity. The obtained LA and LV assessment did not differ in between the participating athletes. The baseline echocardiographic characteristics are presented in Table. Table 1.Baseline anthropometric Ski-Mo characteristics. Ski-Mo Malen= 8 Ski-Mo Femalen= 3 Age (years) 20.5 2.4 19 0 Height (cm) 177.8 4.6 164.0 20.0 Weight (kg) 63.6 6.1 52.1 5.9 BMI (kg/m 2 ) 20.1 1.4 19.3 0.4 resting blood pressure systolic/diastolic (mmHg) 119 6.1 85 3.2 110 5.2 71 2.3 resting heart rate (bpm) 41 3.6 44 2.5 BSA (body surface area m 2 ) 1.79 0.1 1.79 0.1 Data are presented as a median with standard deviation. Abbreviations: cm, centimeter; kg, kilogram; m 2 , square meter; bpm; beats per minute. Bold: anthropometric athlete's characteristics. Table 2. Baseline echocardiographic measurements (mean SD) of the Ski-mountaineering athletes and comparison to the stated control data of the position statement paper of the DGK (German Society of Cardiology, 2020).Ski-Mo Male n= 8 Ski-Mo Female n= 3 Reference Value Male Reference Value Female LV edd (mm) 47.13 4.64 43.67 2.31 42–58 38–52 LV Mass Index (g/m 2 ) 71.38 15.50 67.33 12.35 49–115 43–95 Relative wall Thickness RWT

Ski-mountaineering athletes and comparison to the stated control data of the position statement paper of the DGK (German Society of Cardiology, 2020).Ski-Mo Male n= 8 Ski-Mo Female n= 3 Reference Value Male Reference Value Female LV edd (mm) 47.13 4.64 43.67 2.31 42–58 38–52 LV Mass Index (g/m 2 ) 71.38 15.50 67.33 12.35 49–115 43–95 Relative wall Thickness RWT 0.34 0.05 0.37 0.05 IVSd (mm) 8.25 1.28 7.33 0.58 6–10 6–9 LVPWs (mm) 8.00 0.93 8.00 1.00 6–10 6–9 E/A 1.98 0.32 1.90 0.20 E/E 0 5.08 2.18 5.53 0.62 LAVI (mL/m 2 ) 28.13 8.17 36.00 3.00 RA (cm 2 ) 15.00 2.39 14.00 2.65

Int. J. Environ. Res. Public Health2022,19, 13153 5 of 13 Table 2.Cont. Ski-Mo Male n= 8 Ski-Mo Female n= 3 Reference Value Male Reference Value Female LV EFrest(%) 61.38 4.17 59.00 1.00 52–72 54–72 LV EFpost-stress(%) 70.00 2.88 68.33 0.58 Data are presented as a median with standard deviation. Abbreviations: LV edd, left ventricle enddiastolic size; LV, left ventricular; IVSd, interventricular septal wall thickness at diastole; LVPWd, left ventricular posterior wall thickness at diastole; E/A and E/E 0 , parameters for diastolic function of the left ventricle; LAVI, left atrial volume index; RA, right atrium; LV EF, left ventricular systolic ejection fraction. Bold: echocardiographic parameters. In comparison with data from sedentary control measurements presented by the German Society of Cardiology (DGK) [32] and with previous morphological and functional echocardiographic data from these athletes [7,8], the obtained sport speci c morphological echocardiographic data [LVedd diameter, LV Mass index measurements, interventricular septal wall thickness at diastole (IVSd) and left ventricular posterior wall thickness at diastole (LVPWd), and systolic LV-EF] can be categorized to be in the normal range [7,8]. 3.2. Speckle Tracking Analysis of the Right and Left Heart at Rest and Post-Exercise–Sport-Speci c Functional Cardiac Remodeling In the speckle tracking analysis, normal LV-GLS values at rest ( 21.55 3.44%) and slightly reduced values for LV-GLS post-exercise ( 17.25 3.39%) were elucidated. The difference between rest and post-exercise assessment was signi cant (p= 0.0036), as presented in Figure. No signi cant differences were found for the RV free wall longitudinal deformation (RV FW long.Def. rest 28.17 5.45% vs. RV FW long.Def. post-exercise 26.57 6.24%, p= 0.48) nor for the RV apical four-chamber longitudinal deformation (RV 4C long.Def. rest 23.08 2.09% vs. RV 4C long.Def. post-exercise 21.71 4.89%,p= 0.40) at rest and post-exercise. With respect to standard echocardiographic parameters, LA and LV geometric prop- erties did not show signi cant interindividual differences. The evaluation of functional LA remodeling by the average phasic LA strain (LAS) during all three phases of the atrial cycle revealed signi cant differences in the comparison of resting and post-exercise con- ditions. In this context, across our participating athletes

With respect to standard echocardiographic parameters, LA and LV geometric prop- erties did not show signi cant interindividual differences. The evaluation of functional LA remodeling by the average phasic LA strain (LAS) during all three phases of the atrial cycle revealed signi cant differences in the comparison of resting and post-exercise con- ditions. In this context, across our participating athletes neither the LASr analysis at rest compared to post-exercise strain pattern (LASr rest 51.95 11.55% vs. LASr post-exercise 43.92 11.88%,p= 0.12) nor the LASct analysis at rest compared to post-exercise strain pattern (LASct rest 10.49 7.45% vs. LASct post-exercise 15.46 11.58%,p= 0.24) revealed signi cant differences. Signi cant differences could be elucidated for the LAScd analysis at rest versus post- exercise parameters (LAScd rest 41.45 5.46% vs. LAScd post-exercise 28.45 10.33%, p= 0.0033, as presented in Figure).

Int. J. Environ. Res. Public Health2022,19, 13153 6 of 13Int. J. Environ. Res. Public Health 2022, 19, x FOR PEER REVIEW 6 of 13 Figure 1. Speckle tracking analyses of world elite Ski-Mo professional–Comparison of mean LV- GLS, phasic LA strain and RV strain with significant differences between resting conditions and post-exercise. ** indicates p < 0.01. No significant differences were found for the RV free wall longitudinal deformation (RV FW long.Def. rest −28.17 ± 5.45% vs. RV FW long.Def. post-exercise −26.57 ± 6.24%, p = 0.48) nor for the RV apical four-chamber longitudinal deformation (RV 4C long.Def. rest −23.08 ± 2.09% vs. RV 4C long.Def. post-exercise −21.71 ± 4.89%, p = 0.40) at rest and post- exercise. Figure 1. Speckle tracking analyses of world elite Ski-Mo professional–Comparison of mean LV- GLS, phasic LA strain and RV strain with signi cant differences between resting conditions and post-exercise. ** indicatesp< 0.01. 3.3. Sport-Speci c Functional Cardiac Remodeling–Univariante Relationships between Morphological Echocardiographic Characteristics and Functional Remodeling as Speckle Tracking Analyses No signi cant correlations between LAVI and the athlete's heart strain pattern could be revealed, whereby a negative correlation between LV mass and LV-GLS (p= 0.0195, r = 0.69) and LV-GLS and LV mass Index (p= 0.0253, r = 0.66) at rest could be proven, as presented in Figure.

This study investigates cardiac strain modifications in elite Ski-Mo athletes after maximal exercise.