Long-duration Spaceflight Induces Atrophy in the Left Ventricular Papillary Muscles.

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Cyril Tordeur, Elza Abdessater, Amin Hossein, Francesca Righetti, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5010545/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Nov, 2025 Read the published version in npj Microgravity → Version 1 posted 10 You are reading this latest preprint version Abstract Microgravity exposure induces cardiac deconditioning, primarily due to hypovolemia and inactivity. Animal models suggest microgravity may cause left ventricular (LV) papillary muscle atrophy, but this has not been studied in humans. This study used MRI to assess LV papillary muscle mass and LV morphology and function in nine male cosmonauts before and 6 ± 2 days after long-duration spaceflight (247 ± 90 days). Spaceflight did not affect LV volumes and ejection fraction but increased heart rate (P < 0.001), cardiac output (P = 0.03), and longitudinal strain parameters. There was a 13.6% decrease in LV papillary muscle mass (P = 0.017) with a trend of increase in the LV mass, increased mitral annular diameter (P = 0.004) without mitral leakage, and increased LV sphericity (P = 0.02). These findings suggest LV adapts to space with geometric changes, but microgravity-induced papillary muscle atrophy requires further study for long-term implications. Health sciences/Health care/Medical imaging/Magnetic resonance imaging Biological sciences/Physiology Health sciences/Anatomy Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Exposure to microgravity induces a cranial fluid shift 1 . This partial vascular redistribution leads to an initial atrial expansion 2 and a decrease in total plasma volume 3 . Moreover, the removal of the downward pull of gravitational forces from the Earth causes a reduction in mechanical loading on the longitudinal axis of the heart 4 , 5 . Altogether, without exercise countermeasures, long-term exposure to such conditions leads to a decrease in left ventricular (LV) function, as assessed by transthoracic echocardiography, with a reduction in LV stroke volume (SV) 6 and increased sphericity of the LV cavity 7 . Furthermore, after a few weeks in microgravity, apparent atrophy of the LV was observed using cardiac magnetic resonance imaging (MRI) in the absence of exercise countermeasure 8 . Simulated microgravity through − 6° head-down bed-rest (-6°HDBR) is considered a valid Earth-based model of microgravity because it elicits most of the physiological effects of microgravity exposure through inactivity and a cranial fluid shift 9 – 11 . It induces a decrease in total plasma volume of about 6–15% after a few days to 45 days 11 , 12 . Cardiovascular deconditioning is also an induced effect of -6°HDBR without exercise countermeasures, with supporting evidence of an induced decrease in LV function 13 – 16 , a reduction in LV strain mechanics 17 , and a reduction in LV myocardial mass 18 – 20 . However, no definitive explanation has been provided regarding the mechanisms underlying apparent LV atrophy. Dehydration caused by physiological fluid exchanges provoked by microgravity-induced fluid redistribution, instead of real cellular atrophy, could be the cause of this reduction in LV myocardial mass 21 . Indeed, a return to preflight LV myocardial mass values was observed soon after spaceflight using transthoracic echocardiography 21 . Additionally, the observed LV atrophy could be reproduced under ground-based dehydration condition 21 . The − 6°HDBR model was used to test the effectiveness of countermeasures to prevent cardiovascular deconditioning, resulting in either preservation 18 , 20 , 22 or an increase 19 , 23 in the LV myocardial mass. Recently, a positive effect of exercise countermeasures on the preservation of LV myocardial mass was demonstrated after long-duration spaceflight onboard the International Space Station (ISS) 24 . However, in these previous studies, no specific focus has been placed on the LV papillary muscles (PPM), and LV mass quantification was usually performed by pre- and post-flight measurements using cardiac magnetic resonance imaging (MRI), considering the LV PPM as part of the LV cavity. The only study investigating modifications in LV papillary muscles (PPM) after exposure to microgravity was published by Goldstein et al. in 1992 in a murine animal model 25 : after exposing rats to 14 days of microgravity during the COSMOS 2044 flight, a decrease of 19% in the myofiber cross-sectional area of the LV PPM was observed compared with the ground control. However, no changes in the LV myofiber cross-sectional area were observed, probably because of the short duration of exposure, with no associated measurements of LV functional adaptation. Nevertheless, this study suggests that microgravity affects the PPM differently than the parietal LV myocardium. Anatomically, the LV PPM are two critical structures attaching postero-medially and antero-laterally to the ventricular myocardium and connected to the mitral valve (MV) cusps via the chordae tendineae 26 . The primary role of the PPM is to prevent the inversion or prolapse of the MV leaflets during systole by contracting and maintaining tension on the chordae tendineae, thereby ensuring proper MV closure and unidirectional atrioventricular blood flow. PPMs are therefore essential for the proper functioning of the MV and thus contribute significantly to the LV work 26 – 28 . In clinical practice, quantification of LV myocardial mass using cardiac MRI has previously been reported both including and excluding the PPM in the LV mass computation 29 – 31 . This choice has significant implications, as their inclusion may hinder PPM changes, especially in studies examining the effects of microgravity on the cardiovascular system where small changes in total LV mass are expected. The PPM account for approximately 9% of the total LV myocardial mass 29 , which corresponds to a value comparable to the total LV atrophy reported following microgravity exposure 21 . Thus, excluding PPM from LV myocardial mass quantification is essential for isolating and accurately assessing specific changes in LV mass and PPM morphology. Given the paucity of literature on this subject, there is a significant need to evaluate the impact of potential alterations in PPM in humans exposed to microgravity and to include functional measurements, especially in the context of extended exposure to microgravity. Accordingly, our aim was to use cardiac MRI as a valuable and appropriate imaging modality to assess and quantify changes in the LV PPM and ventricular myocardial mass 32 induced by extended exposure to microgravity in cosmonauts. We hypothesized that the mass of the LV PPM would decrease in cosmonauts after long-term spaceflight, with concomitant modifications in the LV morphology and function as well as changes in the structure of the MV. METHOD STUDY DESIGN Professional cosmonauts assigned to 6-month and longer (long-duration) ISS flights were eligible to participate in this before-after flight investigation. This study was approved by the Erasme University Hospital Ethics Committee (P2017/332/CCBB406201732664), by the Biomedical Ethics Committee of the Institute of Biomedical Problems of the Russian Academy of Sciences from the 20th of June 2018 (#474, Cardiovector 2–3), as well as by the medical boards of all partners of the ISS program and Human Research Multilateral Review Board. The cosmonauts were prospectively recruited on a voluntary basis after providing written informed consent. Cosmonauts flying through missions other than Soyuz missions were excluded due to incompatibility with the logistics of the postflight cardiac imaging protocol. POPULATION DEFINITION In total, 9 male cosmonauts exposed to microgravity during long-duration missions onboard ISS (Expedition 63 to 69, spanning between early 2020 and late 2023) were studied. Among these cosmonauts (mean age: 44 ± 6 y, body height: 1.77 ± 0.05 m, body weight: 82 ± 8 kg, BMI: 26.3 ± 1.8 kg/m 2 ), three participated in a 12-month mission (range: 355 to 371 days), while six were assigned to a 6-month mission (range: 176 to 194 days). These two subgroups were pooled in the context of this study. PROTOCOL MRI acquisitions were performed using 1.5 T or 3.0 T MRI scanner (Magnetom Aero or Magnetom Vida, Siemens, Erlangen, Germany) at the University Hospital of the Moscow State University. Heart rate (HR) was measured on the bedside of the cosmonauts just before MRI acquisition. The cosmonauts were supine during the measurements, and no contrast agents were used. The total MRI time was 60 min. The overall MRI procedure was repeated before (60 − 45 days before launch) and after (6 ± 2 days after landing) spaceflight. During the ISS spaceflight, the cosmonauts followed a strict countermeasure protocol to prevent and counteract the negative effects of weightlessness on cardiovascular and musculoskeletal systems 33 . This protocol includes physical exercises and loading suits used as physical methods to produce an Earth-like fluid distribution, as well as per os water-salt additives used to prevent fluid loss and maintain tolerance to gravitational overload during return to Earth. CARDIAC MAGNETIC RESONANCE IMAGING ACQUISITIONS Conventional retrospective electrocardiography-gated multi-breath-hold balanced steady-state free precession (bSSFP) cine sequences were selected. The scanning protocol, following international guidelines, included several cine sequences: LV two-chamber (2CV) view, LV three-chamber (3CV) view aligned with the center of the LV outflow tract, four-chamber (4CV) view, and LV short-axis stack (SAX) 34 . The scanning range of the short-axis was adjusted to cover the entire LV from the base to the apex during diastole and systole. Cine MRI parameters used for the acquisitions are presented in Table 1 . Table 1 MRI parameters set for the cine acquisition protocols. Parameters Two-chamber, three-chamber, and four-chamber views Left ventricular short-axis stack Repetition time (ms) 36.4 42.4 Echo time (ms) 1.16 1.11 Flip angle (°) 55 54 Field-of-view (mm 2 ) 243 x 300 276 x 340 Spatial resolution (mm 2 ) 1.55 x 1.55 1.77 x 1.77 Cine frames per slice 25 25 Slice thickness (mm) 6 8 Interslice gap (mm) 2 Furthermore, the myocardial tissue was characterized using advanced tissue mapping sequences in three slices (basal, mid-ventricular, and apical) of the LV. Two specific magnetic tissue properties were quantified to compute a parametric mapping: the time constant of longitudinal magnetization recovery without an exogenous contrast agent (native T1), and the time constant of the decay of transverse magnetization (T2). To acquire native T1 mapping, a modified Look Locker Inversion recovery imaging protocol was used in the diastolic phase. A motion correction algorithm was used for the two mapping acquisitions 34 , 35 . The MRI tissue mapping parameters used for acquisition are presented in Table 2 . Table 2 MRI parameters set for the tissue mapping acquisition protocols. Parameters Native T1 mapping T2 mapping Sequence MOLLI T2-prepared bSSFP Echo times (ms) 1.15 1.35 Repetition time (ms) 283.08 219.14 Preparation pulses (ms) 0/25/55 Flip angle (°) 35 12 Number of sets 8 3 Imaging plane SAX SAX Number of slices acquired 3 3 Slice thickness (mm) 8 6 Interslice gap (mm) 20 15 Spatial resolution (mm 2 ) 1.33 x 1.33 1.77 x 1.77 Field-of-view (mm 2 ) 289 x 340 290 x 340 SAX = short-axis view; MOLLI = modified look-locker inversion recovery; bSSFP = balanced steady-state free precession. DATA COLLECTION, REPRODUCTIBILITY, AND ANALYSIS Data collection was performed in Moscow and then transmitted to Brussels for analysis. Data analysis was conducted using CAAS MR Solutions version 5.1.3. (Pie Medical Imaging, Maastricht, The Netherlands). The data generated by this software were then saved in tabular format for statistical analysis. Data handling was designed to ensure that it was impossible to distinguish between pre- and post-flight recordings: all data from all subjects were mixed and analyzed in a fully blinded and randomized manner, with no regard to identity or sequence order. The intra-rater reliability and inter-rater agreement were also assessed by performing the measurements independently by two investigators located in Brussels. The first investigator blindly repeated the procedure with 2 months in-between the two measurements. Left ventricular structure and function For each SAX acquisition, the end-diastolic (ED) and end-systolic (ES) frames, as well as the basal and apical planes, were defined according to the cardiovascular magnetic resonance guidelines 36 . The LV epicardium and endocardium were first segmented using an automatic segmentation tool applied to the images, followed by manual correction using a spline tool. Furthermore, a manual drawing of the contours of the LV PPM was performed. This contouring was conducted based on the following specific standard of practice: no contouring of the myocardium in the LV cavity in slices apically to the insertion point of the PPM on the LV myocardium, no contouring of PPM outside of their physiological anatomical locations (antero-laterally and postero-medially), but contouring on tissue with a concentric displacement when contracting. This standard of practice was defined to exclude LV trabecular tissue and chordae tendineae from the PPM volume. The aforementioned analysis allowed to measure the PPM mass, LV myocardial mass, LV end-diastolic (EDV), and end-systolic (ESV) volumes, as well as the LV SV and LV ejection fraction (EF). Only ED measurements were used to determine the PPM and LV myocardial masses. The LV sphericity index was also computed as the ratio between the short- and long-axis LV dimensions, as described in the literature 37 , 38 . As part of LV function assessment, mitral annular plane systolic excursion (MAPSE) and global longitudinal strain (GLS) were analyzed. The MAPSE was computed as the average between the septal and the lateral diastole-systole displacement of the MV annular plane 39 . This assessment was performed on cine long-axis 4CV images using a semi-automated MV tracking module in the analysis software. Moreover, considering the probable reduction in LV long-axis length due to microgravity exposure, LV longitudinal fractional shortening (LFS) was calculated using the following formula to represent MAPSE as fractional shortening of the LV long-axis 40 , 41 : $$\:\text{L}\text{F}\text{S}=\:\frac{\text{M}\text{A}\text{P}\text{S}\text{E}}{\text{L}\text{V}\:\text{l}\text{o}\text{n}\text{g}\:\text{a}\text{x}\text{i}\text{s}\:\text{l}\text{e}\text{n}\text{g}\text{t}\text{h}}$$ To calculate the global longitudinal strain (GLS), the strain module of the analysis software was used. Cine images were uploaded from long-axis 2CV, 3CV, and 4CV views. The epicardium and endocardium were segmented at the ED and tracked throughout systole using a feature tracking algorithm to detect ventricular deformation, as described in Brandt et al. 42 , 43 . Considering the positive chronotropic effect previously described after spaceflight 44 – 46 and the impact of HR on the measurements of cardiac mechanics 47 , 48 , GLS was corrected by the RR interval, as previously recommended by Modin et al. 49 . Left ventricular tissue mapping Native T1 and T2 mappings were postprocessed according to the latest consensus statements 35 , 36 , 50 . After visual assessment to detect artifacts and significant motion, quantitative analysis was conducted using a single region of interest manually drawn conservatively in the interventricular septum on the mid-cavity short-axis using the grayscale image. Mitral annular diameter The mitral annular diameter was assessed by measuring the linear distance between the mitral leaflet insertion points on the septal and lateral sides of the annulus. This was performed on the long-axis of the 2CV and 4CV views at ED 51 . STATISTICAL ANALYSIS Statistical analysis was performed using GraphPad Prism for macOS 10.2.0. (GraphPad Software, Boston, The United States) and RStudio (Posit Software PBC, Boston, The United States) with R version 4.2.1. Continuous variables were compared using paired t -tests after assessing for outlying values, normality (QQ plot, Shapiro-Wilk, and D’Agostino-Pearson tests), and asserting for a high within-pair Pearson correlation coefficient to justify the use of a large-sample test considering the reduced sample size. Statistical tests diagnostics were made on residuals to assess the reliability of statistical conclusions. For tissue mapping, two different MRI field strength were used: 1.5 T and 3 T. Therefore, only data acquired from cosmonauts tested pre- and post-flight on the same MRI scanner were considered for analysis, thus reaching a sample size of seven instead of nine. These two independent subgroups (1.5 T and 3T) were pooled together for statistical analysis, and the Wilcoxon matched-pair signed-rank test (a non-parametric test) was chosen, because of the bimodal nature of this distribution, to compare the preflight and postflight timepoints for native T1 mapping and T2 mapping. For all features, a reliability assessment was performed to evaluate the intra-rater reliability and inter-rater agreement. All acquisitions were analyzed and considered in these assessments. For this purpose, the intraclass correlation coefficients (ICC) were computed based on a two-way mixed-effects model using two raters by applying the psych library with the function ICC() in R. The measurements from the first rater were taken as the actual measurements used in the statistical tests 52 . Based on the 95% confidence interval of the ICC estimate, values less than 0.5, between 0.5 and 0.75, between 0.75 and 0.9, and greater than 0.90 were considered indicative of poor, moderate, good, and excellent reliability, respectively 52 . Moreover, possible bias between raters was assessed by the Bland-Altman analysis. Correlation analysis was conducted by computing the Pearson correlation coefficient and simple linear regression. Correlation analysis using tissue mapping variables was conducted using the percentage of changes between preflight and postflight considering the previously mentioned pooled distribution. Continuous variables are expressed as the mean ± standard deviation. All tests were two-tailed, and a P value < 0.05 was considered statistically significant. Considering this type of study with a limited number of cosmonauts, a P value < 0.1 was also considered to uncover possible trends. Cohen’s d effect size parameter was computed for all results considered significant or for uncovering possible trends using the rstatix library with the function cohens_d() in R. RESULTS REPRODUCIBILITY ASSESSMENT The intra-rater reliability and inter-rater agreement results of the analyses conducted with the ICC were all between good and excellent (as reported in Tables 3 , 4 , and 5 for the intra-rater and inter-rater analysis). No biases were identified by Bland-Altman and the statistical relationships were the same for all iterations of measurements. CHANGES IN LEFT VENTRICULAR FUNCTION Table 3 lists the results related to the LV function. No significant differences in EDV, ESV, SV, and EF were observed between pre- and post-flight. However, due to a higher HR postflight compared with preflight (59 ± 6 vs. 51 ± 7 bpm; P < 0.001; d = 2.60), increased cardiac output (CO) was observed postflight (6.0 ± 1.0 vs. 5.2 ± 1.3 L/min; P = 0.030; d = 0.88). Moreover, MAPSE (14.1 ± 1.8 vs. 13.3 ± 1.8 mm; P = 0.001; d = 1.12), LFS (14.20 ± 1.30 vs. 13.04 ± 1.14%; P = 0.002; d = 1.47; see Fig. 1 subpanel a), and GLSc (-16.24 ± 2.07 vs. -15.16 ± 2.33%; P = 0.027; d = -0.91; see Fig. 1 subpanel b) increased postflight compared to preflight values. However, the uncorrected GLS for HR did not change. PRE = Preflight; POST = Postflight; POST – PRE = individual POST – PRE difference; LFS = Left ventricular Fractional Shortening; GLSc = Global Longitudinal Strain corrected for RR intervals. The left subpanel “a” represents the evolution of the left ventricular fractional shortening quantified before and after spaceflight (left axis). The right subpanel “b” represents the evolution of left ventricular global longitudinal strain corrected fort RR intervals quantified before and after spaceflight (left axis). Each right subpanel represents individual POST – PRE differences in addition to the mean difference between the two groups with its 95% confidence interval (right axis). Individual values are plotted in overlay (black circles). P value < 0.05 is considered statistically significant. Table 3 Left ventricular function. Parameters Spaceflight Timepoints P value ICCs PRE POST Intra Inter ( n = 9) ( n = 9) EDV (mL) 164.8 ± 24.6 162.6 ± 27.0 0.459 0.97 0.95 ESV (mL) 62.3 ± 16.6 61.3 ± 16.9 0.844 0.89 0.87 SV (mL) 102.5 ± 21.2 101.4 ± 16.8 0.792 0.89 0.88 EF (%) 62.1 ± 8.3 62.5 ± 6.2 0.890 0.89 0.78 HR* (bpm) 51 ± 7 59 ± 6 < 0.001 NA NA CO (L/min) 5.2 ± 1.3 6.0 ± 1.0 0.030 0.94 0.93 MAPSE (mm) 13.3 ± 1.8 14.1 ± 1.8 0.001 0.96 0.84 LFS (%) 13.04 ± 1.14 14.20 ± 1.30 0.002 0.93 0.76 GLS (%) -16.15 ± 1.79 -15.89 ± 1.89 0.645 0.96 0.96 GLSc (%/s (1/2) ) -15.16 ± 2.33 -16.24 ± 2.07 0.027 0.97 0.95 PRE = Preflight; POST = Postflight; ICC = Intraclass Correlation Coefficient; EDV = End Diastolic Volume; ESV = End Systolic Volume; SV = Stroke Volume; EF = Ejection Fraction; HR = Heart Rate; CO = Cardiac Output; MAPSE = Mitral Annular Plane Systolic Excursion; LFS = Longitudinal Fractional Shortening; GLS = Global Longitudinal Strain: GLSc = Global Longitudinal Strain corrected for RR intervals; NA = not applicable. P values reported in bold are considered statistically significant. * Heart Rate was measured on the bedside of the cosmonaut just before the MRI acquisitions. CHANGES IN LEFT VENTRICULAR MORPHOLOGY AND MITRAL-VALVE-RELATED PARAMETERS Table 4 lists the results related to LV morphology. No changes were observed in the LV diameter, but a possible trend toward an increase in LV myocardial mass postflight (150.6 ± 30.1 vs. 137.3 ± 23.5 g; P = 0.083; d = 0.66; see Fig. 2 subpanel a) was observed. Moreover, a decrease in LV length (99.2 ± 8.1 vs. 101.3 ± 8.2 mm; P = 0.020; d = 0.97) and an increase in the LV sphericity index (0.50 ± 0.05 vs. 0.49 ± 0.05; P = 0.020; d = 0.99; see Fig. 3 subpanel a) were observed postflight compared with preflight values. In addition, a 13.6% decrease (relative difference between the average of the preflight and the average of the postflight values) in LV PPM mass (8.7 ± 1.8 vs. 10.1 ± 1.8 g; P = 0.017; d = -1.0; see Fig. 2 subpanel b) was observed compared with preflight values (mean of differences with 95% CI = -1.36 g [-2.42 to -0.32 g]). No changes were found in the mitral annular diameter measured in the 2CV view, whereas a significant increase in mitral annular diameter in the 4CV view (36.8 ± 4.4 vs. 34.8 ± 4.0 mm; P = 0.004; d = 1.33; see Fig. 3 subpanel b) was observed compared with preflight. Table 4 Left ventricular morphology and mitral-valve-related parameters. Parameters Spaceflight Timepoints P value ICCs PRE POST Intra Inter ( n = 9) ( n = 9) Myocardial Mass (g) 137.3 ± 23.5 150.6 ± 30.1 0.083 0.97 0.89 Diameter (mm) 49.5 ± 4.1 49.5 ± 4.5 0.904 0.97 0.96 Length (mm) 101.3 ± 8.2 99.2 ± 8.1 0.020 0.99 0.98 Sphericity Index 0.49 ± 0.05 0.50 ± 0.05 0.020 0.98 0.96 PPM Mass (g) 10.1 ± 1.8 8.7 ± 1.8 0.017 0.97 0.84 MAD 2CV (mm) 40.0 ± 3.9 38.8 ± 4.1 0.187 0.90 0.86 MAD 4CV (mm) 34.8 ± 4.0 36.8 ± 4.4 0.004 0.97 0.91 PRE = Preflight; POST = Postflight; ICC = Intraclass Correlation Coefficient; PPM = Papillary Muscles; MAD = Mitral Annular Diameter; 2CV = two-chamber long-axis view; 4CV = four-chamber long-axis view. P values reported in bold are considered statistically significant and the ones reported in italic are considered as exposing a possible statistical trend. PRE = Preflight; POST = Postflight; POST – PRE = individual POST – PRE difference; LV = Left Ventricle; PPM = Papillary Muscles. The left subpanel “a” represents the evolution of the left ventricular myocardial mass quantified before and after spaceflight (left axis). The right subpanel “b” represents the evolution of the left ventricular papillary muscles mass quantified before and after spaceflight (left axis). Each right subpanel represents individual POST – PRE differences in addition to the mean difference between the two groups with its 95% confidence interval (right axis). Individual values are plotted in overlay (black circles). P value < 0.05 is considered statistically significant and P value < 0.1 is considered to uncover possible trends. PRE = Preflight; POST = Postflight; POST – PRE = individual POST – PRE difference; SI = left ventricular Sphericity Index; MAD = Mitral Annular Diameter measured in four-chamber long-axis view in end-diastole. The left subpanel “a” represents the evolution of the left ventricular sphericity index quantified before and after spaceflight (left axis). The right subpanel “b” represents the evolution of the mitral annular diameter quantified before and after spaceflight (left axis). Each right subpanel represents individual POST – PRE differences in addition to the mean difference between the two groups with its 95% confidence interval (right axis). Individual values are plotted in overlay (black circles). P value < 0.05 is considered statistically significant. CHANGES IN LEFT VENTRICULAR TISSUE PROPERTIES Table 5 presents the results of the LV tissue mapping. No differences were observed in the pooled native T1 mapping relaxation times. However, a possible trend toward an increase in pooled T2 mapping relaxation time was observed postflight compared to preflight values. Table 5 Left ventricular tissue properties. Parameters Spaceflight Timepoints P value ICCs PRE POST Intra Inter ( n = 7) ( n = 7) T1 map 1.5 T (ms) 961.4 ± 18.7 965.4 ± 28.4 0.297 $ 0.99 0.99 3 T (ms) 1144.8 ± 18.6 1202.8 ± 24.1 T2 map 1.5 T (ms) 42.5 ± 1.4 43.6 ± 1.3 0.078 $ 0.97 0.87 3 T (ms) 40.1 ± 0.4 40.6 ± 0.4 PRE = Preflight; POST = Postflight; ICC = Intraclass Correlation Coefficient; T1 map = left ventricular time constant for recovery of longitudinal magnetization; T2 map = left ventricular time constant for the decay of transverse magnetization. P values reported in italic are considered as exposing a possible statistical trend. $ Analysis on pooled 1.5 T ( n = 5) and 3 T ( n = 2) samples. CORRELATIONS No correlations were found between changes in LV PPM mass and mitral annular diameter, LV myocardial mass, LV sphericity index, LV length, and LV functionality parameters, including MAPSE, LFS, GLS, and GLSc. No correlations were found between longitudinal strain parameters and HR, SV, CO, LV myocardial mass, and LV SI. Additionally, a trend toward a positive correlation between changes in native T1 mapping relaxation time and LV myocardial mass was found (R = 0.74, R 2 = 0.54, F(1, 5) = 5.943, P = 0.059) with a fitted linear regression model as follows: Y = 2.820*X + 3.763. DISCUSSION The main new findings of this study evaluating the long-term effect of microgravity exposure on cardiac morphological and functional adaptations using MRI is a decrease in the mass of the LV PPM after spaceflight as well as an increase in the MV annular diameter. Concomitant with these findings, the LV myocardial mass tended to increase compared to preflight measurements. This trend of increase was associated with an improvement in LV systolic function, as reflected by increased MAPSE, LFS, and GLSc. Morphological changes in the LV were also observable after spaceflight, with an increase in the LV sphericity index due to a decrease in the LV longitudinal length from preflight to postflight. However, the LV volume and EF remained stable after spaceflight. Additionally, we a trend of increase in LV T2 mapping relaxation time was observed from preflight to postflight, together with a trend towards a positive correlation between the changes in native T1 mapping relaxation time and in LV myocardial mass. LEFT VENTRICULAR PAPILLARY MUSCLES MASS We observed a 13.6% decrease in LV PPM mass after long-duration spaceflight. This result represents a new finding concerning the adaptations of the heart in humans exposed to long-duration microgravity. Similar findings were reported in animal models. Indeed, in a study by Goldstein et al., two weeks of microgravity exposure in rats led to a 19% decrease in the myofiber cross-sectional area of the LV PPM compared with ground control rats 25 . Based on these results suggesting PPM atrophy observed in rats after spaceflight, two studies were designed to assess whether the function of the atrophic PPM myocardial tissue was impaired and, if so, to investigate the underlying mechanisms 53 , 54 . The authors investigated the changes in LV PPM mass in a simulation of microgravity using a model of tail suspension in rats for 4 weeks and observed a decrease in the developed tension force 53 and the maximal velocity of contraction 54 compared with the control group. The latter study also observed a decrease of 18.7% in the myocardial myofibrillar Ca 2+ -ATPase activity in the tail suspension rats compared to control 54 . This decrease in transport activity could be an underlying explanation of the decrease in maximal velocity of contraction observed in the same study. To our knowledge, the two previous studies are the only ones who have investigated mechanisms behind this reduction in PPM mass in rats. This finding is important because previous research indicated that this atrophy could be associated with a decrease in contractile force generation. From the physiological point of view, a global reduction in mechanical load on the PPM through spherical remodeling of the LV and changes in transmission of force in the structural complex, generated by the interaction between the MV and LV 55 , 56 , could lead to lower stimulation of local mechanoreceptors in the muscle tissue, resulting in decreased synthesis of contractile proteins and consequently muscle atrophy. This atrophy of the PPM could have a direct impact on the contractile properties of the muscle, with possible associated alterations in the excitation-contraction coupling mechanisms. Both mechanisms contributed to the decreased maximal contraction velocity and developed tension force of the PPM. Further work needs to address the implications of exercise countermeasure in this context, knowing the importance of the PPM in the normal function of the MV. Moreover, specific research protocols should deepen the investigation of the mechanisms behind this PPM atrophy associated with microgravity exposure. Indeed, based on what we observed, it appears to be a differential response of the myocardium in the LV, with a tendency toward an increase in LV mass, and the myocardium in the PPM, with a decrease in PPM mass, when exposed to long-duration microgravity with exercise countermeasures. Specific research protocols should address the cellular mechanisms underlying this differential plasticity response when exposed to the same stimuli. Advancing this understanding should help to find ways to address these issues. Undoubtedly, alterations of the LV PPM are known to be one of the clinical starting points of secondary mitral valve prolapse 57 , being the most common cause of primary moderate to severe mitral regurgitation in resource-abundant countries 58 , 59 . Reassuringly, to our current knowledge, none of these clinical manifestations were reported among astronaut crews after spaceflight. MITRAL-VALVE-RELATED PARAMETERS In the present study, mitral annular diameter, measured in long-axis 4CV view, was increased after long-duration exposure to microgravity. Although the same was not observed on the long-axis 2CV view, this constitutes a novel finding regarding the morphology of the mitral valve in the context of long-duration spaceflight, as no other studies have investigated mitral valve dilation after microgravity exposure. MV prolapse and leakage couldn’t be assessed. The decrease in PPM mass and dilation of the MV annulus observed in this study might be the result of adaptation that could lead to MV prolapse either in microgravity or upon return to gravity. Indeed, clinical literature consistently shows links between mitral annular diameter and MV prolapse or regurgitation 60 – 62 . Most importantly, in the context of the present study findings, it is crucial to highlight the work of Izumi et al. and Nordblom et al., who demonstrated that the size and position of the PPM could be implicated in the underlying mechanisms of functional mitral regurgitation 63 , 64 . This clinical literature underscores the need for further studies investigating the relationship between PPM mass and mitral valve function in the context of long-duration spaceflight. Additionally, more attention should be given to MV function on the long-term after long-duration space missions as mitral regurgitation remains asymptomatic for prolonged periods and before symptoms occur, irreversible damages take place 65 , 66 . LEFT VENTRICULAR FUNCTION AND MORPHOLOGY Due to evident material and practical constraints to conduct experiments on astronauts, numerous research studies have focused on the effect of simulated microgravity by -6°HDBR, associated or not with exercise countermeasure, on the LV function and morphology, although relatively few studies have utilized MRI for this purpose. Such evaluations conducted with a longer duration − 6°HDBR of either 21 days 18 , 5 weeks 19 or 70 days 20 associated with exercise countermeasures showed a preservation 18 , 20 or an increase 19 of the LV myocardial mass measured with transthoracic echocardiography compared with the control group without exercise. In the aforementioned studies, exercise countermeasures included continuous exercise, resistance exercise, or a combination of both in addition to high-intensity interval training. Using cardiac MRI, two studies observed a preservation effect of exercise countermeasures with an increase in LV myocardial mass compared with the control without countermeasures, on an 18 days − 6°HDBR 23 or a 21 days − 6° HDBR protocol 22 . Among these studies, two showed that exercise alone, which was used as a countermeasure, could also prevent the decrease in LV EDV through a training-induced plasma volume expantion effect 18 , 20 . However, in other experimental settings, studies have shown that exercise alone was not sufficient to prevent this decrease 19 , 22 , 23 , whereas Shibata et al. demonstrated the benefits of intravenous infusion to restore LV EDV after their − 6°HDBR protocol 23 . This suggests that in order to maintain LV EDV, plasma volume expansion through intravenous infusion could be a countermeasure to be used individually depending on the subject, and effectively this is a known practice used by flight surgeons on immediate return after spaceflight. Only few studies investigated the effects of effective microgravity exposure on the LV function and morphology. Perhonen et al., using MRI, observed a trend of decrease in LV myocardial mass after short-duration spaceflight 8 . On those short duration spaceflights, no countermeasures were used. Based on these observations made on four astronauts, it was suggested that the human heart atrophies in response to decreased physiological loading during short-duration spaceflight. This was confirmed by Summers et al., who observed a decrease in LV myocardial mass and EDV after short-duration spaceflight 21 . Additionally, their study design also included a ground-based study of dehydration to investigate the mechanism underlying the decrease in LV myocardial mass. This control study could reproduce this significant decrease. Based on these combined study designs, Summers et al. demonstrated that the decrease in LV myocardial mass observed in astronauts after short-duration spaceflight was likely due to dehydration rather than cardiac atrophy. Conversely, more recently, Shibata et al. observed no significant changes in LV myocardial mass and volumes after long-duration spaceflight when exercise countermeasures were implemented 24 . Based on these observations, the authors concluded that the exercise countermeasure used onboard the ISS are effective in offsetting reductions in LV mass and volumes during long-duration spaceflight. Nonetheless, it should be noted that the different results reported in these studies may also be caused by differences in the techniques used (echocardiography versus MRI) and their respective limitations, as well as the exact time at which the measurement were performed. The results of the present study regarding LV myocardial mass and volumes align with simulated microgravity and real exposure studies, showing no alterations after long-duration spaceflight with exercise countermeasure. The observed tendency of increased LV myocardial mass in our study could be related to the tailored exercise countermeasure used in the current missions, as also reported by Shibata et al. 24 . In the present study, we observed an improvement in the LV function, as reflected by increased longitudinal strain parameters after spaceflight. On the contrary, prolonged cardiac unloading through − 6°HDBR protocols without exercise as a countermeasure resulted in decreased LV longitudinal strain parameters 17 , 19 , 67 . Additionally, previous studies have shown that LV longitudinal strain parameters decrease with preload reduction 68 and increase with preload elevation 5 , 69 . This preload dependency on LV longitudinal strain parameters is consistent with the Frank-Starling law, in which increased preload leads to enhanced myocardial contractility. As previously demonstrated, exercise training used as a countermeasure in microgravity simulation through − 6°HDBR has been shown to maintain the LV EDV while preserving the LV preload 18 , 20 . Besides this, spaceflight exerts a positive chronotropic effect on the heart 44 – 46 . This increase in HR has a well-known effect on the measurement of cardiac strain, with higher inter- and intra-rater variability in longitudinal strain parameters in the context of dobutamine infusion 47 , 48 . Despite HR-dependent increases in contractility, longitudinal strain decreases with SV as a load-dependent index of LV ejection 70 . In the present study, GLS was corrected for HR 49 to assess the HR-independent longitudinal strain, which increased after spaceflight. Ultimately, two studies investigating long-term exposure to simulated microgravity, using a -6°HDBR setting in combination with exercise as a countermeasure, found preservation of the LV longitudinal strain parameters after bed-rest 19 , 20 . Based on these findings, exercise appears to be an effective method for preventing LV longitudinal functional alteration during simulated microgravity. Interestingly, the increase in GLSc with conserved LV EF observed in our study represents a new findings that requires further investigation. This probably constitutes a compensatory mechanism of LV mechanics to maintain cardiac output, as cardiac performance assessed through strain analysis, particularly longitudinal strain, is more sensitive for detecting changes in myocardial performance beyond LV EF 71 , 72 . Moreover, these results are in line with the preventive effect of exercise on LV functional alterations during spaceflight observed in the present study and Shibata et al. 24 . Exercise countermeasure to microgravity exposure, or in simulation of microgravity, seems effective at preventing LV morphological and functional alterations 19 , 23 , 24 . Countermeasure protocols, including exercises, are commonly followed by cosmonauts who undertake long-duration spaceflights lasting up to 438 days 33 , 73 . The results of the present study suggest that the countermeasure protocol followed by cosmonauts onboard the ISS can effectively preserve LV volumes, mass, and function during long-duration spaceflight. Even though potential differences may be present in the countermeasure protocol used by cosmonauts and the national aeronautics and space administration astronauts included in the study of Shibata et al. 24 , they result in comparable outcomes concerning the LV mass and LV volumes. Moreover, as evaluated by MRI, exercise training protocol on Earth is known to increase the LV myocardial mass 74 – 76 , which is also observed in space, however the latter is accompagned by an increased LV sphericity not seen on Earth 4 , 7 , 74 . We confirmed this physiological adaptation in LV geometry with an increase in LV sphericity index, mainly induced by a decrease in LV length. The mechanism behind LV spherical remodeling, on Earth, may involve a mismatch between mitral valve complex and myocardial longitudinal tissue elongation 56 . In the present study, a trend of increase in LV relaxation time of transverse magnetization or T2 relaxation times was observed. Moreover, a trend toward a positive correlation between changes in native T1 mapping relaxation time and LVmyocardial mass was observed. Luetkens et al. confirmed the influence of physiological hydration changes as a confounder of T1 and T2 relaxation times 77 . They found that dehydration decreased LV myocardial T1 and T2 relaxation times. The inflight per os water-salt additive and immediate postflight plasma volume expansion probably used by cosmonauts could explain the presently observed trend of increase in T2 relaxation times and, associated with exercise countermeasures, the trend toward a positive correlation between changes in native T1 mapping relaxation time and LV myocardial mass. However, the specific effects of plasma volume restoration techniques, which are used to restore LV EDV in the context of microgravity exposure or microgravity simulation, on LV native T1 and T2 relaxation times havenot been directly studied. Further research is needed to fully understand this relationship and its impact on these new findings in the context of microgravity exposure. LIMITATIONS The cardiac MRI method used in this study protocol was adapted for the evaluation of LV PPM mass, besides being the gold standard for the evaluation of the investigated cardiac functional and morphological parameters 32 , 78 , 79 . Indeed, this imaging method offers good spatial and temporal resolution, good soft-tissue contrast, multi-planar capabilities, and lacks ionizing radiation 32 . However, postflight MRI measurements were acquired on average 6 days after landing. Considering the rapid cardiovascular and hemodynamic recovery following return to Earth’s gravitational field 80 , it is possible that the amplitudes of the reported changes would have been larger or that some trends could have become significant if the measurements have been conducted earlier after landing. However, it is not possible to give a final status on the kinetic of reversibility based on the present study. It is important to note that the present cardiac MRI protocols were not specifically designed to evaluate the MV morphology and function. Indeed, other specific MRI acquisition protocols allow for a thorough assessment of the MV morphology and function, including detecting MV prolapse and regurgitation if present 81 . Indeed, the inflight per os water-salt additive and immediate postflight plasma volume expansion probably used by cosmonauts when coming back on Earth. If these interventions were used, they could potentially influence our results. Noteworthy, the total number of subjects recruited in this study is relatively low, which is a common fact in microgravity studies, due to obvious recruitment and logistical constraints. However, our results could have significant importance considering the small number of studies investigating cardiac adaptations to actual microgravity exposure during long-duration spaceflight and the growing interest in spaceflight becoming accessible to a more diverse population. Additionally, for a comprehensive assessment of the effects of long-duration spaceflight on the heart, a multidisciplinary approach combining advanced cardiac imaging, molecular, and cellular analyses would be warranted. CONCLUSION AND RESEARCH PERSPECTIVES In conclusion, our study demonstrates that a 6-month or longer exposure to microgravity on the ISS, associated to exercise countermeasure, induces the reduction of the LV PPM mass but not of the LV mass. Concomitant with mitral annular dilation, this atrophy could lead to subclinical alterations of the MV function, particularly when the gravitational field is restored by returning to Earth or landing on another planet subject to a partial gravity field. However, because of the limitations of the present MRI protocols, conclusions regarding MV function could not be fully investigated. Despite the PPM atrophy, the LV seems to adapts to microgravity-induced physiological adaptation in geometry, maintaining unchanged EDV and ESV, SV, and EF, along with increased longitudinal strain parameters. Future research with larger cohorts is needed to elucidate the causes and consequences of the microgravity-induced LV PPM atrophy and mitral annular dilation. Moreover, specific clinical MRI acquisition protocols will be required to assess the impact of these adaptations on the possibility of functional short- or long-term postflight MV alteration. Additionally, it is important to mention the possibility of conducting a follow-up with these cohorts to see if the mass of the PPM would recover over time. Declarations ACKNOWLEDGMENTS The authors thank the Belgian Federal Science Policy Office (BELSPO) for the provision of financial support in the framework of the PRODEX Programme of the European Space Agency (ESA) under contract number [PEA 4000110826]. C.T. and A.H. were supported through this framework. The research project was also carried out with the funding of the State Corporation Roscosmos and within the framework of the basic theme of the Russian Academy of Sciences by basic programs FMFR-2024-0042. E.A. was supported by Fonds Erasme. E.G.C. and F.R. were supported by the Italian Space Agency (contracts 2022-09-U.0 and 2022-10-U.0). Moreover, we would like to express our gratitude and appreciation to the cosmonauts who took part in this research project, as well as to Pie Medical Imaging for their continuous support. AUTHOR AFFILIATIONS AND CONTRIBUTIONS AFFILIATIONS Laboratory of Physics and Physiology (LPHYS), Department of Cardiology, Hôpital Universitaire de Bruxelles - Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium Cyril Tordeur, Elza Abdessater, Amin Hossein, Vitalie Faoro, Philippe van de Borne & Jeremy Rabineau Brussels Laboratory of the Universe (BLU), Université libre de Bruxelles, Brussels, Belgium Cyril Tordeur, Elza Abdessater, Amin Hossein, Vitalie Faoro, Philippe van de Borne & Jeremy Rabineau Department of Radiology, Medical Educational and Scientific Center University Hospital, Lomonosov Moscow State University, Moscow, Russia Valentin Sinitsyn & Elena Mershina Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia Elena Luchitskaya Electronics, Information and Bioengineering Dpt., Politecnico di Milano, Milan, Italy Francesca Righetti & Enrico Giuanluca Caiani IRCCS Istituto Auxologico Italiano, San luca Hospital, Milan, Italy Enrico Giuanluca Caiani Cardio-Pulmonary Exercise Physiology Laboratory, Faculty of Human Movement Sciences, Université libre de Bruxelles, Brussels, Belgium Vitalie Faoro & Jeremy Rabineau Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany Jens Tank Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, Ontario, Canada Jeremy Rabineau CONTRIBUTIONS V.F., J.R., P.V.D.B., J.T., E.G.C., E.L., V.S., and E.M. defined the project. J.R. wrote and obtained ethical approval for the study. E.M. collected data on the cosmonauts. C.T. and E.A. performed post-processing MRI analysis. C.T. performed statistical analysis. C.T., E.A., F.R., A.H., V.F., P.V.D.B., and J.R. contributed to the interpretation of the results. C.T. drafted the first version of the manuscript. All the authors critically revised the manuscript and gave their approval for publication. COMPETING INTERESTS DECLARATIONS The authors declare no competing interests. DATA AVAILABILITY The datasets used and/or analysed during the current study are available from the corresponding author on a reasonable request. References Shen, M. & Frishman, W. H. Effects of Spaceflight on Cardiovascular Physiology and Health. Cardiol Rev 27, 122–126 (2019). https://doi.org:10.1097/CRD.0000000000000236 Caiani, E. G. et al. Objective evaluation of changes in left ventricular and atrial volumes during parabolic flight using real-time three-dimensional echocardiography. 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J Hypertens 29, 137–143 (2011). https://doi.org:10.1097/HJH.0b013e32833f5e01 Choi, J. O. et al. Effect of preload on left ventricular longitudinal strain by 2D speckle tracking. Echocardiography 25, 873–879 (2008). https://doi.org:10.1111/j.1540-8175.2008.00707.x Schneider, C., Forsythe, L., Somauroo, J., George, K. & Oxborough, D. The impact of preload reduction with head-up tilt testing on longitudinal and transverse left ventricular mechanics: a study utilizing deformation volume analysis. Echo Res Pract 5, 11–18 (2018). https://doi.org:10.1530/ERP-17-0064 Mak, S., Van Spall, H. G., Wainstein, R. V. & Sasson, Z. Strain, strain rate, and the force frequency relationship in patients with and without heart failure. J Am Soc Echocardiogr 25, 341–348 (2012). https://doi.org:10.1016/j.echo.2011.11.008 Smiseth, O. A., Torp, H., Opdahl, A., Haugaa, K. H. & Urheim, S. Myocardial strain imaging: how useful is it in clinical decision making? Eur Heart J 37, 1196–1207 (2016). https://doi.org:10.1093/eurheartj/ehv529 Potter, E. & Marwick, T. H. Assessment of Left Ventricular Function by Echocardiography: The Case for Routinely Adding Global Longitudinal Strain to Ejection Fraction. JACC Cardiovasc Imaging 11, 260–274 (2018). https://doi.org:10.1016/j.jcmg.2017.11.017 Kozlovskaya, I. B., Grigoriev, A. I. & Stepantzov, V. I. Countermeasure of the negative effects of weightlessness on physical systems in long-term space flights. Acta Astronaut 36, 661–668 (1995). https://doi.org:10.1016/0094-5765(95)00156-5 Spence, A. L. et al. A prospective randomised longitudinal MRI study of left ventricular adaptation to endurance and resistance exercise training in humans. J Physiol 589, 5443–5452 (2011). https://doi.org:10.1113/jphysiol.2011.217125 Vogelsang, T. W. et al. Effect of eight weeks of endurance exercise training on right and left ventricular volume and mass in untrained obese subjects: a longitudinal MRI study. Scand J Med Sci Sports 18, 354–359 (2008). https://doi.org:10.1111/j.1600-0838.2007.00706.x Batterham, A. M., George, K. P., Birch, K. M., Pennell, D. J. & Myerson, S. G. Growth of left ventricular mass with military basic training in army recruits. Med Sci Sports Exerc 43, 1295–1300 (2011). https://doi.org:10.1249/MSS.0b013e3182093300 Luetkens, J. A. et al. Influence of hydration status on cardiovascular magnetic resonance myocardial T1 and T2 relaxation time assessment: an intraindividual study in healthy subjects. J Cardiovasc Magn Reson 22, 63 (2020). https://doi.org:10.1186/s12968-020-00661-9 Salerno, M. & Kramer, C. M. Advances in parametric mapping with CMR imaging. JACC Cardiovasc Imaging 6, 806–822 (2013). https://doi.org:10.1016/j.jcmg.2013.05.005 Rajiah, P. S., Francois, C. J. & Leiner, T. Cardiac MRI: State of the Art. Radiology 307, e223008 (2023). https://doi.org:10.1148/radiol.223008 Rabineau, J. et al. Cardiovascular deconditioning and impact of artificial gravity during 60-day head-down bed rest-Insights from 4D flow cardiac MRI. Front Physiol 13, 944587 (2022). https://doi.org:10.3389/fphys.2022.944587 Garg, P. et al. Assessment of mitral valve regurgitation by cardiovascular magnetic resonance imaging. Nat Rev Cardiol 17, 298–312 (2020). https://doi.org:10.1038/s41569-019-0305-z Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 12 Nov, 2025 Read the published version in npj Microgravity → Version 1 posted Editorial decision: Revision requested 18 Mar, 2025 Reviews received at journal 12 Mar, 2025 Reviewers agreed at journal 26 Feb, 2025 Reviews received at journal 29 Oct, 2024 Reviewers agreed at journal 07 Oct, 2024 Reviewers agreed at journal 07 Oct, 2024 Reviewers invited by journal 24 Sep, 2024 Editor assigned by journal 16 Sep, 2024 Submission checks completed at journal 06 Sep, 2024 First submitted to journal 31 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5010545","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":360697645,"identity":"9df5ba79-44c0-4e4f-b91a-9e8571254c64","order_by":0,"name":"Cyril Tordeur","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYJCCAw/AVAIQVzDIGDDwEKElgcEAquUMAw9RWhjgWhjbiNDCPyP3IdCWP3Lm7cnHpCvnHeYxZ+A9+ACfFokb6QYghxnLnHmWJnl222Eeywa+ZAN8Wgwk0sB+SZwhkWMm2QjUYnCAx0yCSC353yQb54C1mP8g1hY2ycYGiC34dDBInHkG1GJgbCzB88zYsuFYOo9lM18yXofxt6cxf/hQIScnwZ788GZDjbWcOXvvwQ94rRFIADkPWYQZr3qQNQcIqRgFo2AUjIIRDwC95EOzS0nCmgAAAABJRU5ErkJggg==","orcid":"","institution":"Université Libre de Bruxelles","correspondingAuthor":true,"prefix":"","firstName":"Cyril","middleName":"","lastName":"Tordeur","suffix":""},{"id":360697647,"identity":"7afe8864-5113-4178-be6d-6ac53f6b9475","order_by":1,"name":"Elza Abdessater","email":"","orcid":"","institution":"Université Libre de Bruxelles","correspondingAuthor":false,"prefix":"","firstName":"Elza","middleName":"","lastName":"Abdessater","suffix":""},{"id":360697650,"identity":"1ec2b88b-c833-48d9-8eb1-a5983a3526ae","order_by":2,"name":"Amin Hossein","email":"","orcid":"","institution":"Université Libre de Bruxelles","correspondingAuthor":false,"prefix":"","firstName":"Amin","middleName":"","lastName":"Hossein","suffix":""},{"id":360697653,"identity":"6ab68820-c3c1-4432-8f96-9a4d9ea14236","order_by":3,"name":"Francesca Righetti","email":"","orcid":"","institution":"Politecnico di Milano","correspondingAuthor":false,"prefix":"","firstName":"Francesca","middleName":"","lastName":"Righetti","suffix":""},{"id":360697655,"identity":"d2bc6396-45e9-40aa-91d2-2bb47fa8757c","order_by":4,"name":"Valentin Sinitsyn","email":"","orcid":"","institution":"Lomonosov Moscow State University","correspondingAuthor":false,"prefix":"","firstName":"Valentin","middleName":"","lastName":"Sinitsyn","suffix":""},{"id":360697656,"identity":"6a094356-dcfa-492b-9fe3-945717fbad9c","order_by":5,"name":"Elena Mershina","email":"","orcid":"","institution":"Lomonosov Moscow State University","correspondingAuthor":false,"prefix":"","firstName":"Elena","middleName":"","lastName":"Mershina","suffix":""},{"id":360697657,"identity":"9b2dac6c-fc41-48bb-88af-95761e4ba332","order_by":6,"name":"Elena Luchitskaya","email":"","orcid":"","institution":"Institute of Biomedical Problems","correspondingAuthor":false,"prefix":"","firstName":"Elena","middleName":"","lastName":"Luchitskaya","suffix":""},{"id":360697659,"identity":"6f3bb629-4ede-4a4d-adcf-c5694fca67dd","order_by":7,"name":"Enrico G. Caiani","email":"","orcid":"","institution":"Politecnico di Milano","correspondingAuthor":false,"prefix":"","firstName":"Enrico","middleName":"G.","lastName":"Caiani","suffix":""},{"id":360697660,"identity":"21aa32af-8dc7-4767-b08d-87f9f5d965fb","order_by":8,"name":"Vitalie Faoro","email":"","orcid":"","institution":"Université Libre de Bruxelles","correspondingAuthor":false,"prefix":"","firstName":"Vitalie","middleName":"","lastName":"Faoro","suffix":""},{"id":360697661,"identity":"21131a90-e587-44b3-8bef-3b7635b77839","order_by":9,"name":"Jens Tank","email":"","orcid":"","institution":"German Aerospace Center","correspondingAuthor":false,"prefix":"","firstName":"Jens","middleName":"","lastName":"Tank","suffix":""},{"id":360697662,"identity":"2b83acd6-ce50-411b-ab3b-f8a033f457f8","order_by":10,"name":"Philippe van de Borne","email":"","orcid":"","institution":"Université Libre de Bruxelles","correspondingAuthor":false,"prefix":"","firstName":"Philippe","middleName":"van","lastName":"de Borne","suffix":""},{"id":360697664,"identity":"e9ba8204-1ec6-41ae-8310-932f05f495b6","order_by":11,"name":"Jérémy Rabineau","email":"","orcid":"","institution":"Université Libre de Bruxelles","correspondingAuthor":false,"prefix":"","firstName":"Jérémy","middleName":"","lastName":"Rabineau","suffix":""}],"badges":[],"createdAt":"2024-08-31 21:24:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5010545/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5010545/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41526-025-00531-7","type":"published","date":"2025-11-12T15:58:20+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":65931005,"identity":"d42f1eb4-4b30-44df-a1c2-ad5c41e14f09","added_by":"auto","created_at":"2024-10-04 13:55:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":241206,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLeft ventricular shortening.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePRE = Preflight; POST = Postflight; POST – PRE = individual POST – PRE difference; LFS = Left ventricular Fractional Shortening; GLSc = Global Longitudinal Strain corrected for RR intervals. The left subpanel “a” represents the evolution of the left ventricular fractional shortening quantified before and after spaceflight (left axis). The right subpanel “b” represents the evolution of left ventricular global longitudinal strain corrected fort RR intervals quantified before and after spaceflight (left axis). Each right subpanel represents individual POST – PRE differences in addition to the mean difference between the two groups with its 95% confidence interval (right axis). Individual values are plotted in overlay (black circles). Pvalue \u0026lt; 0.05 is considered statistically significant.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-5010545/v1/3c3ce666ed890d2b296daae9.png"},{"id":65930259,"identity":"ca328f59-8a5c-479a-a011-d280c9baea70","added_by":"auto","created_at":"2024-10-04 13:47:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":255752,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLeft ventricular and papillary muscles masses.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePRE = Preflight; POST = Postflight; POST – PRE = individual POST – PRE difference; LV = Left Ventricle; PPM = Papillary Muscles. The left subpanel “a” represents the evolution of the left ventricular myocardial mass quantified before and after spaceflight (left axis). The right subpanel “b” represents the evolution of the left ventricular papillary muscles mass quantified before and after spaceflight (left axis). Each right subpanel represents individual POST – PRE differences in addition to the mean difference between the two groups with its 95% confidence interval (right axis). Individual values are plotted in overlay (black circles). Pvalue \u0026lt; 0.05 is considered statistically significant and Pvalue \u0026lt; 0.1 is considered to uncover possible trends.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-5010545/v1/a0cc709040d86f58b4d957ab.png"},{"id":65930261,"identity":"3ba63c5c-04d7-4891-bd87-e70e16c14889","added_by":"auto","created_at":"2024-10-04 13:47:03","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":250800,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLeft ventricular structural changes.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePRE = Preflight; POST = Postflight; POST – PRE = individual POST – PRE difference; SI = left ventricular Sphericity Index; MAD = Mitral Annular Diameter measured in four-chamber long-axis view in end-diastole. The left subpanel “a” represents the evolution of the left ventricular sphericity index quantified before and after spaceflight (left axis). The right subpanel “b” represents the evolution of the mitral annular diameter quantified before and after spaceflight (left axis). Each right subpanel represents individual POST – PRE differences in addition to the mean difference between the two groups with its 95% confidence interval (right axis). Individual values are plotted in overlay (black circles). \u003cem\u003eP\u003c/em\u003e value \u0026lt; 0.05 is considered statistically significant.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-5010545/v1/3d5611b7d941014280c92a0a.png"},{"id":96105092,"identity":"4793a80d-47a5-423b-843d-d728718f41d9","added_by":"auto","created_at":"2025-11-17 16:08:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2267362,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5010545/v1/dff40efa-7d8f-4d58-b96a-ee2ebf84fdb1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Long-duration Spaceflight Induces Atrophy in the Left Ventricular Papillary Muscles.","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eExposure to microgravity induces a cranial fluid shift \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. This partial vascular redistribution leads to an initial atrial expansion \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e and a decrease in total plasma volume \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Moreover, the removal of the downward pull of gravitational forces from the Earth causes a reduction in mechanical loading on the longitudinal axis of the heart \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Altogether, without exercise countermeasures, long-term exposure to such conditions leads to a decrease in left ventricular (LV) function, as assessed by transthoracic echocardiography, with a reduction in LV stroke volume (SV) \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e and increased sphericity of the LV cavity \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Furthermore, after a few weeks in microgravity, apparent atrophy of the LV was observed using cardiac magnetic resonance imaging (MRI) in the absence of exercise countermeasure \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSimulated microgravity through \u0026minus;\u0026thinsp;6\u0026deg; head-down bed-rest (-6\u0026deg;HDBR) is considered a valid Earth-based model of microgravity because it elicits most of the physiological effects of microgravity exposure through inactivity and a cranial fluid shift \u003csup\u003e\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. It induces a decrease in total plasma volume of about 6\u0026ndash;15% after a few days to 45 days \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Cardiovascular deconditioning is also an induced effect of -6\u0026deg;HDBR without exercise countermeasures, with supporting evidence of an induced decrease in LV function \u003csup\u003e\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e, a reduction in LV strain mechanics \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e, and a reduction in LV myocardial mass \u003csup\u003e\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHowever, no definitive explanation has been provided regarding the mechanisms underlying apparent LV atrophy. Dehydration caused by physiological fluid exchanges provoked by microgravity-induced fluid redistribution, instead of real cellular atrophy, could be the cause of this reduction in LV myocardial mass \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Indeed, a return to preflight LV myocardial mass values was observed soon after spaceflight using transthoracic echocardiography \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Additionally, the observed LV atrophy could be reproduced under ground-based dehydration condition \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. The \u0026minus;\u0026thinsp;6\u0026deg;HDBR model was used to test the effectiveness of countermeasures to prevent cardiovascular deconditioning, resulting in either preservation \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e or an increase \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e in the LV myocardial mass. Recently, a positive effect of exercise countermeasures on the preservation of LV myocardial mass was demonstrated after long-duration spaceflight onboard the International Space Station (ISS) \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHowever, in these previous studies, no specific focus has been placed on the LV papillary muscles (PPM), and LV mass quantification was usually performed by pre- and post-flight measurements using cardiac magnetic resonance imaging (MRI), considering the LV PPM as part of the LV cavity. The only study investigating modifications in LV papillary muscles (PPM) after exposure to microgravity was published by Goldstein et al. in 1992 in a murine animal model \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e: after exposing rats to 14 days of microgravity during the COSMOS 2044 flight, a decrease of 19% in the myofiber cross-sectional area of the LV PPM was observed compared with the ground control. However, no changes in the LV myofiber cross-sectional area were observed, probably because of the short duration of exposure, with no associated measurements of LV functional adaptation. Nevertheless, this study suggests that microgravity affects the PPM differently than the parietal LV myocardium. Anatomically, the LV PPM are two critical structures attaching postero-medially and antero-laterally to the ventricular myocardium and connected to the mitral valve (MV) cusps via the chordae tendineae \u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. The primary role of the PPM is to prevent the inversion or prolapse of the MV leaflets during systole by contracting and maintaining tension on the chordae tendineae, thereby ensuring proper MV closure and unidirectional atrioventricular blood flow. PPMs are therefore essential for the proper functioning of the MV and thus contribute significantly to the LV work \u003csup\u003e\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn clinical practice, quantification of LV myocardial mass using cardiac MRI has previously been reported both including and excluding the PPM in the LV mass computation \u003csup\u003e\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. This choice has significant implications, as their inclusion may hinder PPM changes, especially in studies examining the effects of microgravity on the cardiovascular system where small changes in total LV mass are expected. The PPM account for approximately 9% of the total LV myocardial mass \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e, which corresponds to a value comparable to the total LV atrophy reported following microgravity exposure \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Thus, excluding PPM from LV myocardial mass quantification is essential for isolating and accurately assessing specific changes in LV mass and PPM morphology.\u003c/p\u003e \u003cp\u003eGiven the paucity of literature on this subject, there is a significant need to evaluate the impact of potential alterations in PPM in humans exposed to microgravity and to include functional measurements, especially in the context of extended exposure to microgravity. Accordingly, our aim was to use cardiac MRI as a valuable and appropriate imaging modality to assess and quantify changes in the LV PPM and ventricular myocardial mass \u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e induced by extended exposure to microgravity in cosmonauts. We hypothesized that the mass of the LV PPM would decrease in cosmonauts after long-term spaceflight, with concomitant modifications in the LV morphology and function as well as changes in the structure of the MV.\u003c/p\u003e"},{"header":"METHOD","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSTUDY DESIGN\u003c/h2\u003e \u003cp\u003eProfessional cosmonauts assigned to 6-month and longer (long-duration) ISS flights were eligible to participate in this before-after flight investigation. This study was approved by the Erasme University Hospital Ethics Committee (P2017/332/CCBB406201732664), by the Biomedical Ethics Committee of the Institute of Biomedical Problems of the Russian Academy of Sciences from the 20th of June 2018 (#474, Cardiovector 2\u0026ndash;3), as well as by the medical boards of all partners of the ISS program and Human Research Multilateral Review Board. The cosmonauts were prospectively recruited on a voluntary basis after providing written informed consent. Cosmonauts flying through missions other than Soyuz missions were excluded due to incompatibility with the logistics of the postflight cardiac imaging protocol.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePOPULATION DEFINITION\u003c/h2\u003e \u003cp\u003eIn total, 9 male cosmonauts exposed to microgravity during long-duration missions onboard ISS (Expedition 63 to 69, spanning between early 2020 and late 2023) were studied. Among these cosmonauts (mean age: 44\u0026thinsp;\u0026plusmn;\u0026thinsp;6 y, body height: 1.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 m, body weight: 82\u0026thinsp;\u0026plusmn;\u0026thinsp;8 kg, BMI: 26.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8 kg/m\u003csup\u003e2\u003c/sup\u003e), three participated in a 12-month mission (range: 355 to 371 days), while six were assigned to a 6-month mission (range: 176 to 194 days). These two subgroups were pooled in the context of this study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePROTOCOL\u003c/h2\u003e \u003cp\u003eMRI acquisitions were performed using 1.5 T or 3.0 T MRI scanner (Magnetom Aero or Magnetom Vida, Siemens, Erlangen, Germany) at the University Hospital of the Moscow State University. Heart rate (HR) was measured on the bedside of the cosmonauts just before MRI acquisition. The cosmonauts were supine during the measurements, and no contrast agents were used. The total MRI time was 60 min. The overall MRI procedure was repeated before (60\u0026thinsp;\u0026minus;\u0026thinsp;45 days before launch) and after (6\u0026thinsp;\u0026plusmn;\u0026thinsp;2 days after landing) spaceflight.\u003c/p\u003e \u003cp\u003eDuring the ISS spaceflight, the cosmonauts followed a strict countermeasure protocol to prevent and counteract the negative effects of weightlessness on cardiovascular and musculoskeletal systems \u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. This protocol includes physical exercises and loading suits used as physical methods to produce an Earth-like fluid distribution, as well as per os water-salt additives used to prevent fluid loss and maintain tolerance to gravitational overload during return to Earth.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eCARDIAC MAGNETIC RESONANCE IMAGING ACQUISITIONS\u003c/h2\u003e \u003cp\u003eConventional retrospective electrocardiography-gated multi-breath-hold balanced steady-state free precession (bSSFP) cine sequences were selected. The scanning protocol, following international guidelines, included several cine sequences: LV two-chamber (2CV) view, LV three-chamber (3CV) view aligned with the center of the LV outflow tract, four-chamber (4CV) view, and LV short-axis stack (SAX) \u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. The scanning range of the short-axis was adjusted to cover the entire LV from the base to the apex during diastole and systole. Cine MRI parameters used for the acquisitions are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMRI parameters set for the cine acquisition protocols.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTwo-chamber, three-chamber, and four-chamber views\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLeft ventricular short-axis stack\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRepetition time (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEcho time (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFlip angle (\u0026deg;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eField-of-view (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e243 x 300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e276 x 340\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpatial resolution (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.55 x 1.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.77 x 1.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCine frames per slice\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSlice thickness (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterslice gap (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFurthermore, the myocardial tissue was characterized using advanced tissue mapping sequences in three slices (basal, mid-ventricular, and apical) of the LV. Two specific magnetic tissue properties were quantified to compute a parametric mapping: the time constant of longitudinal magnetization recovery without an exogenous contrast agent (native T1), and the time constant of the decay of transverse magnetization (T2). To acquire native T1 mapping, a modified Look Locker Inversion recovery imaging protocol was used in the diastolic phase. A motion correction algorithm was used for the two mapping acquisitions \u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. The MRI tissue mapping parameters used for acquisition are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMRI parameters set for the tissue mapping acquisition protocols.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNative T1 mapping\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT2 mapping\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSequence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMOLLI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT2-prepared bSSFP\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEcho times (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRepetition time (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e283.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e219.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreparation pulses (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0/25/55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFlip angle (\u0026deg;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of sets\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImaging plane\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSAX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSAX\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of slices acquired\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSlice thickness (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterslice gap (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpatial resolution (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.33 x 1.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.77 x 1.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eField-of-view (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e289 x 340\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e290 x 340\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSAX\u0026thinsp;=\u0026thinsp;short-axis view; MOLLI\u0026thinsp;=\u0026thinsp;modified look-locker inversion recovery; bSSFP\u0026thinsp;=\u0026thinsp;balanced steady-state free precession.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eDATA COLLECTION, REPRODUCTIBILITY, AND ANALYSIS\u003c/h2\u003e \u003cp\u003eData collection was performed in Moscow and then transmitted to Brussels for analysis. Data analysis was conducted using CAAS MR Solutions version 5.1.3. (Pie Medical Imaging, Maastricht, The Netherlands). The data generated by this software were then saved in tabular format for statistical analysis. Data handling was designed to ensure that it was impossible to distinguish between pre- and post-flight recordings: all data from all subjects were mixed and analyzed in a fully blinded and randomized manner, with no regard to identity or sequence order. The intra-rater reliability and inter-rater agreement were also assessed by performing the measurements independently by two investigators located in Brussels. The first investigator blindly repeated the procedure with 2 months in-between the two measurements.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eLeft ventricular structure and function\u003c/h2\u003e \u003cp\u003eFor each SAX acquisition, the end-diastolic (ED) and end-systolic (ES) frames, as well as the basal and apical planes, were defined according to the cardiovascular magnetic resonance guidelines \u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. The LV epicardium and endocardium were first segmented using an automatic segmentation tool applied to the images, followed by manual correction using a spline tool.\u003c/p\u003e \u003cp\u003eFurthermore, a manual drawing of the contours of the LV PPM was performed. This contouring was conducted based on the following specific standard of practice: no contouring of the myocardium in the LV cavity in slices apically to the insertion point of the PPM on the LV myocardium, no contouring of PPM outside of their physiological anatomical locations (antero-laterally and postero-medially), but contouring on tissue with a concentric displacement when contracting. This standard of practice was defined to exclude LV trabecular tissue and chordae tendineae from the PPM volume.\u003c/p\u003e \u003cp\u003eThe aforementioned analysis allowed to measure the PPM mass, LV myocardial mass, LV end-diastolic (EDV), and end-systolic (ESV) volumes, as well as the LV SV and LV ejection fraction (EF). Only ED measurements were used to determine the PPM and LV myocardial masses. The LV sphericity index was also computed as the ratio between the short- and long-axis LV dimensions, as described in the literature \u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAs part of LV function assessment, mitral annular plane systolic excursion (MAPSE) and global longitudinal strain (GLS) were analyzed. The MAPSE was computed as the average between the septal and the lateral diastole-systole displacement of the MV annular plane \u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e. This assessment was performed on cine long-axis 4CV images using a semi-automated MV tracking module in the analysis software. Moreover, considering the probable reduction in LV long-axis length due to microgravity exposure, LV longitudinal fractional shortening (LFS) was calculated using the following formula to represent MAPSE as fractional shortening of the LV long-axis \u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:\\text{L}\\text{F}\\text{S}=\\:\\frac{\\text{M}\\text{A}\\text{P}\\text{S}\\text{E}}{\\text{L}\\text{V}\\:\\text{l}\\text{o}\\text{n}\\text{g}\\:\\text{a}\\text{x}\\text{i}\\text{s}\\:\\text{l}\\text{e}\\text{n}\\text{g}\\text{t}\\text{h}}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eTo calculate the global longitudinal strain (GLS), the strain module of the analysis software was used. Cine images were uploaded from long-axis 2CV, 3CV, and 4CV views. The epicardium and endocardium were segmented at the ED and tracked throughout systole using a feature tracking algorithm to detect ventricular deformation, as described in Brandt et al. \u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e. Considering the positive chronotropic effect previously described after spaceflight \u003csup\u003e\u003cspan additionalcitationids=\"CR45\" citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e and the impact of HR on the measurements of cardiac mechanics \u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e, GLS was corrected by the RR interval, as previously recommended by Modin et al. \u003csup\u003e\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eLeft ventricular tissue mapping\u003c/h3\u003e\n\u003cp\u003eNative T1 and T2 mappings were postprocessed according to the latest consensus statements \u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e. After visual assessment to detect artifacts and significant motion, quantitative analysis was conducted using a single region of interest manually drawn conservatively in the interventricular septum on the mid-cavity short-axis using the grayscale image.\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eMitral annular diameter\u003c/h2\u003e \u003cp\u003eThe mitral annular diameter was assessed by measuring the linear distance between the mitral leaflet insertion points on the septal and lateral sides of the annulus. This was performed on the long-axis of the 2CV and 4CV views at ED \u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSTATISTICAL ANALYSIS\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using GraphPad Prism for macOS 10.2.0. (GraphPad Software, Boston, The United States) and RStudio (Posit Software PBC, Boston, The United States) with R version 4.2.1. Continuous variables were compared using paired \u003cem\u003et\u003c/em\u003e-tests after assessing for outlying values, normality (QQ plot, Shapiro-Wilk, and D\u0026rsquo;Agostino-Pearson tests), and asserting for a high within-pair Pearson correlation coefficient to justify the use of a large-sample test considering the reduced sample size. Statistical tests diagnostics were made on residuals to assess the reliability of statistical conclusions. For tissue mapping, two different MRI field strength were used: 1.5 T and 3 T. Therefore, only data acquired from cosmonauts tested pre- and post-flight on the same MRI scanner were considered for analysis, thus reaching a sample size of seven instead of nine. These two independent subgroups (1.5 T and 3T) were pooled together for statistical analysis, and the Wilcoxon matched-pair signed-rank test (a non-parametric test) was chosen, because of the bimodal nature of this distribution, to compare the preflight and postflight timepoints for native T1 mapping and T2 mapping.\u003c/p\u003e \u003cp\u003eFor all features, a reliability assessment was performed to evaluate the intra-rater reliability and inter-rater agreement. All acquisitions were analyzed and considered in these assessments. For this purpose, the intraclass correlation coefficients (ICC) were computed based on a two-way mixed-effects model using two raters by applying the \u003cem\u003epsych\u003c/em\u003e library with the function \u003cem\u003eICC()\u003c/em\u003e in R. The measurements from the first rater were taken as the actual measurements used in the statistical tests \u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e. Based on the 95% confidence interval of the ICC estimate, values less than 0.5, between 0.5 and 0.75, between 0.75 and 0.9, and greater than 0.90 were considered indicative of poor, moderate, good, and excellent reliability, respectively \u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e. Moreover, possible bias between raters was assessed by the Bland-Altman analysis. Correlation analysis was conducted by computing the Pearson correlation coefficient and simple linear regression. Correlation analysis using tissue mapping variables was conducted using the percentage of changes between preflight and postflight considering the previously mentioned pooled distribution.\u003c/p\u003e \u003cp\u003eContinuous variables are expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. All tests were two-tailed, and a \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Considering this type of study with a limited number of cosmonauts, a \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.1 was also considered to uncover possible trends. Cohen\u0026rsquo;s \u003cem\u003ed\u003c/em\u003e effect size parameter was computed for all results considered significant or for uncovering possible trends using the \u003cem\u003erstatix\u003c/em\u003e library with the function \u003cem\u003ecohens_d()\u003c/em\u003e in R.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eREPRODUCIBILITY ASSESSMENT\u003c/h2\u003e \u003cp\u003eThe intra-rater reliability and inter-rater agreement results of the analyses conducted with the ICC were all between good and excellent (as reported in Tables \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, and \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e for the intra-rater and inter-rater analysis). No biases were identified by Bland-Altman and the statistical relationships were the same for all iterations of measurements.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eCHANGES IN LEFT VENTRICULAR FUNCTION\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e lists the results related to the LV function. No significant differences in EDV, ESV, SV, and EF were observed between pre- and post-flight. However, due to a higher HR postflight compared with preflight (59\u0026thinsp;\u0026plusmn;\u0026thinsp;6 vs. 51\u0026thinsp;\u0026plusmn;\u0026thinsp;7 bpm; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2.60), increased cardiac output (CO) was observed postflight (6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 vs. 5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3 L/min; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030; \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.88). Moreover, MAPSE (14.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8 vs. 13.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8 mm; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001; \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.12), LFS (14.20\u0026thinsp;\u0026plusmn;\u0026thinsp;1.30 vs. 13.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002; \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.47; see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e subpanel a), and GLSc (-16.24\u0026thinsp;\u0026plusmn;\u0026thinsp;2.07 vs. -15.16\u0026thinsp;\u0026plusmn;\u0026thinsp;2.33%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.027; \u003cem\u003ed\u003c/em\u003e = -0.91; see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e subpanel b) increased postflight compared to preflight values. However, the uncorrected GLS for HR did not change.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePRE\u0026thinsp;=\u0026thinsp;Preflight; POST\u0026thinsp;=\u0026thinsp;Postflight; POST \u0026ndash; PRE\u0026thinsp;=\u0026thinsp;individual POST \u0026ndash; PRE difference; LFS\u0026thinsp;=\u0026thinsp;Left ventricular Fractional Shortening; GLSc\u0026thinsp;=\u0026thinsp;Global Longitudinal Strain corrected for RR intervals. The left subpanel \u0026ldquo;a\u0026rdquo; represents the evolution of the left ventricular fractional shortening quantified before and after spaceflight (left axis). The right subpanel \u0026ldquo;b\u0026rdquo; represents the evolution of left ventricular global longitudinal strain corrected fort RR intervals quantified before and after spaceflight (left axis). Each right subpanel represents individual POST \u0026ndash; PRE differences in addition to the mean difference between the two groups with its 95% confidence interval (right axis). Individual values are plotted in overlay (black circles). \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 is considered statistically significant.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLeft ventricular function.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"2\" nameend=\"c2\" namest=\"c1\" rowspan=\"3\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003eSpaceflight Timepoints\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c12\" namest=\"c10\"\u003e \u003cp\u003eICCs\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePRE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePOST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIntra\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eInter\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEDV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e164.8\u0026thinsp;\u0026plusmn;\u0026thinsp;24.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e162.6\u0026thinsp;\u0026plusmn;\u0026thinsp;27.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.459\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e62.3\u0026thinsp;\u0026plusmn;\u0026thinsp;16.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e61.3\u0026thinsp;\u0026plusmn;\u0026thinsp;16.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.844\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e102.5\u0026thinsp;\u0026plusmn;\u0026thinsp;21.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e101.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.792\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e62.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e62.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.890\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(bpm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e51\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e59\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(L/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.030\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMAPSE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e13.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e14.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLFS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e13.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e14.20\u0026thinsp;\u0026plusmn;\u0026thinsp;1.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGLS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-16.15\u0026thinsp;\u0026plusmn;\u0026thinsp;1.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e-15.89\u0026thinsp;\u0026plusmn;\u0026thinsp;1.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.645\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGLSc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(%/s\u003csup\u003e(1/2)\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-15.16\u0026thinsp;\u0026plusmn;\u0026thinsp;2.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e-16.24\u0026thinsp;\u0026plusmn;\u0026thinsp;2.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.027\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePRE\u0026thinsp;=\u0026thinsp;Preflight; POST\u0026thinsp;=\u0026thinsp;Postflight; ICC\u0026thinsp;=\u0026thinsp;Intraclass Correlation Coefficient; EDV\u0026thinsp;=\u0026thinsp;End Diastolic Volume; ESV\u0026thinsp;=\u0026thinsp;End Systolic Volume; SV\u0026thinsp;=\u0026thinsp;Stroke Volume; EF\u0026thinsp;=\u0026thinsp;Ejection Fraction; HR\u0026thinsp;=\u0026thinsp;Heart Rate; CO\u0026thinsp;=\u0026thinsp;Cardiac Output; MAPSE\u0026thinsp;=\u0026thinsp;Mitral Annular Plane Systolic Excursion; LFS\u0026thinsp;=\u0026thinsp;Longitudinal Fractional Shortening; GLS\u0026thinsp;=\u0026thinsp;Global Longitudinal Strain: GLSc\u0026thinsp;=\u0026thinsp;Global Longitudinal Strain corrected for RR intervals; NA\u0026thinsp;=\u0026thinsp;not applicable. \u003cem\u003eP\u003c/em\u003e values reported in bold are considered statistically significant. * Heart Rate was measured on the bedside of the cosmonaut just before the MRI acquisitions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eCHANGES IN LEFT VENTRICULAR MORPHOLOGY AND MITRAL-VALVE-RELATED PARAMETERS\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e lists the results related to LV morphology. No changes were observed in the LV diameter, but a possible trend toward an increase in LV myocardial mass postflight (150.6\u0026thinsp;\u0026plusmn;\u0026thinsp;30.1 vs. 137.3\u0026thinsp;\u0026plusmn;\u0026thinsp;23.5 g; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.083; \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.66; see Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e subpanel a) was observed. Moreover, a decrease in LV length (99.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1 vs. 101.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2 mm; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020; \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.97) and an increase in the LV sphericity index (0.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 vs. 0.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020; \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.99; see Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e subpanel a) were observed postflight compared with preflight values. In addition, a 13.6% decrease (relative difference between the average of the preflight and the average of the postflight values) in LV PPM mass (8.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8 vs. 10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8 g; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017; \u003cem\u003ed\u003c/em\u003e = -1.0; see Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e subpanel b) was observed compared with preflight values (mean of differences with 95% CI = -1.36 g [-2.42 to -0.32 g]). No changes were found in the mitral annular diameter measured in the 2CV view, whereas a significant increase in mitral annular diameter in the 4CV view (36.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4 vs. 34.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0 mm; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004; \u003cem\u003ed\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.33; see Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e subpanel b) was observed compared with preflight.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLeft ventricular morphology and mitral-valve-related parameters.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"2\" nameend=\"c2\" namest=\"c1\" rowspan=\"3\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003eSpaceflight Timepoints\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c12\" namest=\"c10\"\u003e \u003cp\u003eICCs\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePRE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePOST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIntra\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eInter\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyocardial Mass\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e137.3\u0026thinsp;\u0026plusmn;\u0026thinsp;23.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e150.6\u0026thinsp;\u0026plusmn;\u0026thinsp;30.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003e0.083\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e49.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e49.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.904\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e101.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e99.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.020\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSphericity Index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e0.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.020\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePPM Mass\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e8.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMAD 2CV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e40.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e38.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMAD 4CV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e34.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e36.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePRE\u0026thinsp;=\u0026thinsp;Preflight; POST\u0026thinsp;=\u0026thinsp;Postflight; ICC\u0026thinsp;=\u0026thinsp;Intraclass Correlation Coefficient; PPM\u0026thinsp;=\u0026thinsp;Papillary Muscles; MAD\u0026thinsp;=\u0026thinsp;Mitral Annular Diameter; 2CV\u0026thinsp;=\u0026thinsp;two-chamber long-axis view; 4CV\u0026thinsp;=\u0026thinsp;four-chamber long-axis view. \u003cem\u003eP\u003c/em\u003e values reported in bold are considered statistically significant and the ones reported in italic are considered as exposing a possible statistical trend.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePRE\u0026thinsp;=\u0026thinsp;Preflight; POST\u0026thinsp;=\u0026thinsp;Postflight; POST \u0026ndash; PRE\u0026thinsp;=\u0026thinsp;individual POST \u0026ndash; PRE difference; LV\u0026thinsp;=\u0026thinsp;Left Ventricle; PPM\u0026thinsp;=\u0026thinsp;Papillary Muscles. The left subpanel \u0026ldquo;a\u0026rdquo; represents the evolution of the left ventricular myocardial mass quantified before and after spaceflight (left axis). The right subpanel \u0026ldquo;b\u0026rdquo; represents the evolution of the left ventricular papillary muscles mass quantified before and after spaceflight (left axis). Each right subpanel represents individual POST \u0026ndash; PRE differences in addition to the mean difference between the two groups with its 95% confidence interval (right axis). Individual values are plotted in overlay (black circles). \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 is considered statistically significant and \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.1 is considered to uncover possible trends.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePRE\u0026thinsp;=\u0026thinsp;Preflight; POST\u0026thinsp;=\u0026thinsp;Postflight; POST \u0026ndash; PRE\u0026thinsp;=\u0026thinsp;individual POST \u0026ndash; PRE difference; SI\u0026thinsp;=\u0026thinsp;left ventricular Sphericity Index; MAD\u0026thinsp;=\u0026thinsp;Mitral Annular Diameter measured in four-chamber long-axis view in end-diastole. The left subpanel \u0026ldquo;a\u0026rdquo; represents the evolution of the left ventricular sphericity index quantified before and after spaceflight (left axis). The right subpanel \u0026ldquo;b\u0026rdquo; represents the evolution of the mitral annular diameter quantified before and after spaceflight (left axis). Each right subpanel represents individual POST \u0026ndash; PRE differences in addition to the mean difference between the two groups with its 95% confidence interval (right axis). Individual values are plotted in overlay (black circles). \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 is considered statistically significant.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eCHANGES IN LEFT VENTRICULAR TISSUE PROPERTIES\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e presents the results of the LV tissue mapping. No differences were observed in the pooled native T1 mapping relaxation times. However, a possible trend toward an increase in pooled T2 mapping relaxation time was observed postflight compared to preflight values.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLeft ventricular tissue properties.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"13\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" morerows=\"2\" nameend=\"c3\" namest=\"c1\" rowspan=\"3\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eSpaceflight Timepoints\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c13\" namest=\"c11\"\u003e \u003cp\u003eICCs\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePRE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePOST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIntra\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eInter\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eT1 map\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.5 T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e961.4\u0026thinsp;\u0026plusmn;\u0026thinsp;18.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e965.4\u0026thinsp;\u0026plusmn;\u0026thinsp;28.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.297\u003csup\u003e$\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1144.8\u0026thinsp;\u0026plusmn;\u0026thinsp;18.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1202.8\u0026thinsp;\u0026plusmn;\u0026thinsp;24.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eT2 map\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.5 T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e43.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003e0.078\u003c/em\u003e\u003csup\u003e$\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e40.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePRE\u0026thinsp;=\u0026thinsp;Preflight; POST\u0026thinsp;=\u0026thinsp;Postflight; ICC\u0026thinsp;=\u0026thinsp;Intraclass Correlation Coefficient; T1 map\u0026thinsp;=\u0026thinsp;left ventricular time constant for recovery of longitudinal magnetization; T2 map\u0026thinsp;=\u0026thinsp;left ventricular time constant for the decay of transverse magnetization. \u003cem\u003eP\u003c/em\u003e values reported in italic are considered as exposing a possible statistical trend. \u003csup\u003e$\u003c/sup\u003e Analysis on pooled 1.5 T (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5) and 3 T (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2) samples.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eCORRELATIONS\u003c/h2\u003e \u003cp\u003eNo correlations were found between changes in LV PPM mass and mitral annular diameter, LV myocardial mass, LV sphericity index, LV length, and LV functionality parameters, including MAPSE, LFS, GLS, and GLSc. No correlations were found between longitudinal strain parameters and HR, SV, CO, LV myocardial mass, and LV SI. Additionally, a trend toward a positive correlation between changes in native T1 mapping relaxation time and LV myocardial mass was found (R\u0026thinsp;=\u0026thinsp;0.74, R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.54, F(1, 5)\u0026thinsp;=\u0026thinsp;5.943, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.059) with a fitted linear regression model as follows: Y\u0026thinsp;=\u0026thinsp;2.820*X\u0026thinsp;+\u0026thinsp;3.763.\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe main new findings of this study evaluating the long-term effect of microgravity exposure on cardiac morphological and functional adaptations using MRI is a decrease in the mass of the LV PPM after spaceflight as well as an increase in the MV annular diameter. Concomitant with these findings, the LV myocardial mass tended to increase compared to preflight measurements. This trend of increase was associated with an improvement in LV systolic function, as reflected by increased MAPSE, LFS, and GLSc. Morphological changes in the LV were also observable after spaceflight, with an increase in the LV sphericity index due to a decrease in the LV longitudinal length from preflight to postflight. However, the LV volume and EF remained stable after spaceflight. Additionally, we a trend of increase in LV T2 mapping relaxation time was observed from preflight to postflight, together with a trend towards a positive correlation between the changes in native T1 mapping relaxation time and in LV myocardial mass.\u003c/p\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eLEFT VENTRICULAR PAPILLARY MUSCLES MASS\u003c/h2\u003e \u003cp\u003eWe observed a 13.6% decrease in LV PPM mass after long-duration spaceflight. This result represents a new finding concerning the adaptations of the heart in humans exposed to long-duration microgravity.\u003c/p\u003e \u003cp\u003eSimilar findings were reported in animal models. Indeed, in a study by Goldstein et al., two weeks of microgravity exposure in rats led to a 19% decrease in the myofiber cross-sectional area of the LV PPM compared with ground control rats \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Based on these results suggesting PPM atrophy observed in rats after spaceflight, two studies were designed to assess whether the function of the atrophic PPM myocardial tissue was impaired and, if so, to investigate the underlying mechanisms \u003csup\u003e\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e,\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e. The authors investigated the changes in LV PPM mass in a simulation of microgravity using a model of tail suspension in rats for 4 weeks and observed a decrease in the developed tension force \u003csup\u003e\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u003c/sup\u003e and the maximal velocity of contraction \u003csup\u003e\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e compared with the control group. The latter study also observed a decrease of 18.7% in the myocardial myofibrillar Ca\u003csup\u003e2+\u003c/sup\u003e-ATPase activity in the tail suspension rats compared to control \u003csup\u003e\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e. This decrease in transport activity could be an underlying explanation of the decrease in maximal velocity of contraction observed in the same study.\u003c/p\u003e \u003cp\u003eTo our knowledge, the two previous studies are the only ones who have investigated mechanisms behind this reduction in PPM mass in rats. This finding is important because previous research indicated that this atrophy could be associated with a decrease in contractile force generation. From the physiological point of view, a global reduction in mechanical load on the PPM through spherical remodeling of the LV and changes in transmission of force in the structural complex, generated by the interaction between the MV and LV \u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e,\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u003c/sup\u003e, could lead to lower stimulation of local mechanoreceptors in the muscle tissue, resulting in decreased synthesis of contractile proteins and consequently muscle atrophy. This atrophy of the PPM could have a direct impact on the contractile properties of the muscle, with possible associated alterations in the excitation-contraction coupling mechanisms. Both mechanisms contributed to the decreased maximal contraction velocity and developed tension force of the PPM. Further work needs to address the implications of exercise countermeasure in this context, knowing the importance of the PPM in the normal function of the MV.\u003c/p\u003e \u003cp\u003eMoreover, specific research protocols should deepen the investigation of the mechanisms behind this PPM atrophy associated with microgravity exposure. Indeed, based on what we observed, it appears to be a differential response of the myocardium in the LV, with a tendency toward an increase in LV mass, and the myocardium in the PPM, with a decrease in PPM mass, when exposed to long-duration microgravity with exercise countermeasures. Specific research protocols should address the cellular mechanisms underlying this differential plasticity response when exposed to the same stimuli. Advancing this understanding should help to find ways to address these issues. Undoubtedly, alterations of the LV PPM are known to be one of the clinical starting points of secondary mitral valve prolapse \u003csup\u003e\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e\u003c/sup\u003e, being the most common cause of primary moderate to severe mitral regurgitation in resource-abundant countries \u003csup\u003e\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e,\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e\u003c/sup\u003e. Reassuringly, to our current knowledge, none of these clinical manifestations were reported among astronaut crews after spaceflight.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eMITRAL-VALVE-RELATED PARAMETERS\u003c/h2\u003e \u003cp\u003eIn the present study, mitral annular diameter, measured in long-axis 4CV view, was increased after long-duration exposure to microgravity. Although the same was not observed on the long-axis 2CV view, this constitutes a novel finding regarding the morphology of the mitral valve in the context of long-duration spaceflight, as no other studies have investigated mitral valve dilation after microgravity exposure. MV prolapse and leakage couldn’t be assessed. The decrease in PPM mass and dilation of the MV annulus observed in this study might be the result of adaptation that could lead to MV prolapse either in microgravity or upon return to gravity. Indeed, clinical literature consistently shows links between mitral annular diameter and MV prolapse or regurgitation \u003csup\u003e\u003cspan additionalcitationids=\"CR61\" citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e–\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e\u003c/sup\u003e. Most importantly, in the context of the present study findings, it is crucial to highlight the work of Izumi et al. and Nordblom et al., who demonstrated that the size and position of the PPM could be implicated in the underlying mechanisms of functional mitral regurgitation \u003csup\u003e\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e,\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e\u003c/sup\u003e. This clinical literature underscores the need for further studies investigating the relationship between PPM mass and mitral valve function in the context of long-duration spaceflight. Additionally, more attention should be given to MV function on the long-term after long-duration space missions as mitral regurgitation remains asymptomatic for prolonged periods and before symptoms occur, irreversible damages take place \u003csup\u003e\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e,\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eLEFT VENTRICULAR FUNCTION AND MORPHOLOGY\u003c/h2\u003e \u003cp\u003eDue to evident material and practical constraints to conduct experiments on astronauts, numerous research studies have focused on the effect of simulated microgravity by -6°HDBR, associated or not with exercise countermeasure, on the LV function and morphology, although relatively few studies have utilized MRI for this purpose. Such evaluations conducted with a longer duration − 6°HDBR of either 21 days \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e, 5 weeks \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e or 70 days \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e associated with exercise countermeasures showed a preservation \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e or an increase \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e of the LV myocardial mass measured with transthoracic echocardiography compared with the control group without exercise. In the aforementioned studies, exercise countermeasures included continuous exercise, resistance exercise, or a combination of both in addition to high-intensity interval training. Using cardiac MRI, two studies observed a preservation effect of exercise countermeasures with an increase in LV myocardial mass compared with the control without countermeasures, on an 18 days − 6°HDBR\u003c/p\u003e \u003cp\u003e \u003csup\u003e \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e \u003c/sup\u003e or a 21 days − 6° HDBR protocol \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Among these studies, two showed that exercise alone, which was used as a countermeasure, could also prevent the decrease in LV EDV through a training-induced plasma volume expantion effect \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. However, in other experimental settings, studies have shown that exercise alone was not sufficient to prevent this decrease \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e, whereas Shibata et al. demonstrated the benefits of intravenous infusion to restore LV EDV after their − 6°HDBR protocol \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. This suggests that in order to maintain LV EDV, plasma volume expansion through intravenous infusion could be a countermeasure to be used individually depending on the subject, and effectively this is a known practice used by flight surgeons on immediate return after spaceflight. Only few studies investigated the effects of effective microgravity exposure on the LV function and morphology. Perhonen et al., using MRI, observed a trend of decrease in LV myocardial mass after short-duration spaceflight \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. On those short duration spaceflights, no countermeasures were used. Based on these observations made on four astronauts, it was suggested that the human heart atrophies in response to decreased physiological loading during short-duration spaceflight. This was confirmed by Summers et al., who observed a decrease in LV myocardial mass and EDV after short-duration spaceflight \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Additionally, their study design also included a ground-based study of dehydration to investigate the mechanism underlying the decrease in LV myocardial mass. This control study could reproduce this significant decrease. Based on these combined study designs, Summers et al. demonstrated that the decrease in LV myocardial mass observed in astronauts after short-duration spaceflight was likely due to dehydration rather than cardiac atrophy. Conversely, more recently, Shibata et al. observed no significant changes in LV myocardial mass and volumes after long-duration spaceflight when exercise countermeasures were implemented \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. Based on these observations, the authors concluded that the exercise countermeasure used onboard the ISS are effective in offsetting reductions in LV mass and volumes during long-duration spaceflight. Nonetheless, it should be noted that the different results reported in these studies may also be caused by differences in the techniques used (echocardiography versus MRI) and their respective limitations, as well as the exact time at which the measurement were performed.\u003c/p\u003e \u003cp\u003eThe results of the present study regarding LV myocardial mass and volumes align with simulated microgravity and real exposure studies, showing no alterations after long-duration spaceflight with exercise countermeasure. The observed tendency of increased LV myocardial mass in our study could be related to the tailored exercise countermeasure used in the current missions, as also reported by Shibata et al. \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the present study, we observed an improvement in the LV function, as reflected by increased longitudinal strain parameters after spaceflight. On the contrary, prolonged cardiac unloading through − 6°HDBR protocols without exercise as a countermeasure resulted in decreased LV longitudinal strain parameters \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e\u003c/sup\u003e. Additionally, previous studies have shown that LV longitudinal strain parameters decrease with preload reduction \u003csup\u003e\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e\u003c/sup\u003e and increase with preload elevation \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e\u003c/sup\u003e. This preload dependency on LV longitudinal strain parameters is consistent with the Frank-Starling law, in which increased preload leads to enhanced myocardial contractility. As previously demonstrated, exercise training used as a countermeasure in microgravity simulation through − 6°HDBR has been shown to maintain the LV EDV while preserving the LV preload \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Besides this, spaceflight exerts a positive chronotropic effect on the heart \u003csup\u003e\u003cspan additionalcitationids=\"CR45\" citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e–\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e. This increase in HR has a well-known effect on the measurement of cardiac strain, with higher inter- and intra-rater variability in longitudinal strain parameters in the context of dobutamine infusion \u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e. Despite HR-dependent increases in contractility, longitudinal strain decreases with SV as a load-dependent index of LV ejection \u003csup\u003e\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e\u003c/sup\u003e. In the present study, GLS was corrected for HR \u003csup\u003e\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e to assess the HR-independent longitudinal strain, which increased after spaceflight. Ultimately, two studies investigating long-term exposure to simulated microgravity, using a -6°HDBR setting in combination with exercise as a countermeasure, found preservation of the LV longitudinal strain parameters after bed-rest \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Based on these findings, exercise appears to be an effective method for preventing LV longitudinal functional alteration during simulated microgravity. Interestingly, the increase in GLSc with conserved LV EF observed in our study represents a new findings that requires further investigation. This probably constitutes a compensatory mechanism of LV mechanics to maintain cardiac output, as cardiac performance assessed through strain analysis, particularly longitudinal strain, is more sensitive for detecting changes in myocardial performance beyond LV EF \u003csup\u003e\u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e,\u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e\u003c/sup\u003e. Moreover, these results are in line with the preventive effect of exercise on LV functional alterations during spaceflight observed in the present study and Shibata et al. \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eExercise countermeasure to microgravity exposure, or in simulation of microgravity, seems effective at preventing LV morphological and functional alterations \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. Countermeasure protocols, including exercises, are commonly followed by cosmonauts who undertake long-duration spaceflights lasting up to 438 days \u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e,\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e\u003c/sup\u003e. The results of the present study suggest that the countermeasure protocol followed by cosmonauts onboard the ISS can effectively preserve LV volumes, mass, and function during long-duration spaceflight. Even though potential differences may be present in the countermeasure protocol used by cosmonauts and the national aeronautics and space administration astronauts included in the study of Shibata et al. \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e, they result in comparable outcomes concerning the LV mass and LV volumes. Moreover, as evaluated by MRI, exercise training protocol on Earth is known to increase the LV myocardial mass \u003csup\u003e\u003cspan additionalcitationids=\"CR75\" citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e–\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e\u003c/sup\u003e, which is also observed in space, however the latter is accompagned by an increased LV sphericity not seen on Earth \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e\u003c/sup\u003e. We confirmed this physiological adaptation in LV geometry with an increase in LV sphericity index, mainly induced by a decrease in LV length. The mechanism behind LV spherical remodeling, on Earth, may involve a mismatch between mitral valve complex and myocardial longitudinal tissue elongation \u003csup\u003e\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the present study, a trend of increase in LV relaxation time of transverse magnetization or T2 relaxation times was observed. Moreover, a trend toward a positive correlation between changes in native T1 mapping relaxation time and LVmyocardial mass was observed. Luetkens et al. confirmed the influence of physiological hydration changes as a confounder of T1 and T2 relaxation times \u003csup\u003e\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e\u003c/sup\u003e. They found that dehydration decreased LV myocardial T1 and T2 relaxation times. The inflight per os water-salt additive and immediate postflight plasma volume expansion probably used by cosmonauts could explain the presently observed trend of increase in T2 relaxation times and, associated with exercise countermeasures, the trend toward a positive correlation between changes in native T1 mapping relaxation time and LV myocardial mass. However, the specific effects of plasma volume restoration techniques, which are used to restore LV EDV in the context of microgravity exposure or microgravity simulation, on LV native T1 and T2 relaxation times havenot been directly studied. Further research is needed to fully understand this relationship and its impact on these new findings in the context of microgravity exposure.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eLIMITATIONS\u003c/h2\u003e \u003cp\u003eThe cardiac MRI method used in this study protocol was adapted for the evaluation of LV PPM mass, besides being the gold standard for the evaluation of the investigated cardiac functional and morphological parameters \u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e,\u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e79\u003c/span\u003e\u003c/sup\u003e. Indeed, this imaging method offers good spatial and temporal resolution, good soft-tissue contrast, multi-planar capabilities, and lacks ionizing radiation \u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. However, postflight MRI measurements were acquired on average 6 days after landing. Considering the rapid cardiovascular and hemodynamic recovery following return to Earth’s gravitational field \u003csup\u003e\u003cspan citationid=\"CR80\" class=\"CitationRef\"\u003e80\u003c/span\u003e\u003c/sup\u003e, it is possible that the amplitudes of the reported changes would have been larger or that some trends could have become significant if the measurements have been conducted earlier after landing. However, it is not possible to give a final status on the kinetic of reversibility based on the present study.\u003c/p\u003e \u003cp\u003eIt is important to note that the present cardiac MRI protocols were not specifically designed to evaluate the MV morphology and function. Indeed, other specific MRI acquisition protocols allow for a thorough assessment of the MV morphology and function, including detecting MV prolapse and regurgitation if present \u003csup\u003e\u003cspan citationid=\"CR81\" class=\"CitationRef\"\u003e81\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIndeed, the inflight per os water-salt additive and immediate postflight plasma volume expansion probably used by cosmonauts when coming back on Earth. If these interventions were used, they could potentially influence our results.\u003c/p\u003e \u003cp\u003eNoteworthy, the total number of subjects recruited in this study is relatively low, which is a common fact in microgravity studies, due to obvious recruitment and logistical constraints. However, our results could have significant importance considering the small number of studies investigating cardiac adaptations to actual microgravity exposure during long-duration spaceflight and the growing interest in spaceflight becoming accessible to a more diverse population.\u003c/p\u003e \u003cp\u003eAdditionally, for a comprehensive assessment of the effects of long-duration spaceflight on the heart, a multidisciplinary approach combining advanced cardiac imaging, molecular, and cellular analyses would be warranted.\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"CONCLUSION AND RESEARCH PERSPECTIVES","content":"\u003cp\u003eIn conclusion, our study demonstrates that a 6-month or longer exposure to microgravity on the ISS, associated to exercise countermeasure, induces the reduction of the LV PPM mass but not of the LV mass. Concomitant with mitral annular dilation, this atrophy could lead to subclinical alterations of the MV function, particularly when the gravitational field is restored by returning to Earth or landing on another planet subject to a partial gravity field. However, because of the limitations of the present MRI protocols, conclusions regarding MV function could not be fully investigated. Despite the PPM atrophy, the LV seems to adapts to microgravity-induced physiological adaptation in geometry, maintaining unchanged EDV and ESV, SV, and EF, along with increased longitudinal strain parameters.\u003c/p\u003e\u003cp\u003eFuture research with larger cohorts is needed to elucidate the causes and consequences of the microgravity-induced LV PPM atrophy and mitral annular dilation. Moreover, specific clinical MRI acquisition protocols will be required to assess the impact of these adaptations on the possibility of functional short- or long-term postflight MV alteration. Additionally, it is important to mention the possibility of conducting a follow-up with these cohorts to see if the mass of the PPM would recover over time.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the Belgian Federal Science Policy Office (BELSPO) for the provision of financial support in the framework of the PRODEX Programme of the European Space Agency (ESA) under contract number [PEA\u0026nbsp;4000110826]. C.T. and A.H. were supported through this framework. The research project was also carried out with the funding of the State Corporation Roscosmos and within the framework of the basic theme of the Russian Academy of Sciences by basic programs\u0026nbsp;FMFR-2024-0042. E.A. was supported by Fonds Erasme. E.G.C. and F.R. were supported by the Italian Space Agency (contracts 2022-09-U.0 and 2022-10-U.0). Moreover, we would like to express our gratitude and appreciation to the cosmonauts who took part in this research project, as well as to Pie Medical Imaging for their continuous support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR AFFILIATIONS AND CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAFFILIATIONS\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLaboratory of Physics and Physiology (LPHYS), Department of Cardiology, H\u0026ocirc;pital Universitaire de Bruxelles - Erasme Hospital, Universit\u0026eacute; libre de Bruxelles, Brussels, Belgium\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCyril Tordeur, Elza Abdessater, Amin Hossein, Vitalie Faoro, Philippe van de Borne \u0026amp; Jeremy Rabineau\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBrussels Laboratory of the Universe (BLU), Universit\u0026eacute; libre de Bruxelles, Brussels, Belgium\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCyril Tordeur, Elza Abdessater, Amin Hossein, Vitalie Faoro, Philippe van de Borne \u0026amp; Jeremy Rabineau\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDepartment of Radiology, Medical Educational and Scientific Center University Hospital, Lomonosov Moscow State University, Moscow, Russia\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eValentin Sinitsyn \u0026amp; Elena Mershina\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eElena Luchitskaya\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eElectronics, Information and Bioengineering Dpt., Politecnico di Milano, Milan, Italy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrancesca Righetti \u0026amp; Enrico Giuanluca Caiani\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIRCCS Istituto Auxologico Italiano, San luca Hospital, Milan, Italy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEnrico Giuanluca Caiani\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCardio-Pulmonary Exercise Physiology Laboratory, Faculty of Human Movement Sciences, Universit\u0026eacute; libre de Bruxelles, Brussels, Belgium\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVitalie Faoro \u0026amp; Jeremy Rabineau\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJens Tank\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDepartment of Kinesiology and Health Sciences, University of Waterloo, Waterloo, Ontario, Canada\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJeremy Rabineau\u003c/p\u003e\n\u003cp\u003eCONTRIBUTIONS\u003c/p\u003e\n\u003cp\u003eV.F., J.R., P.V.D.B., J.T., E.G.C., E.L., V.S., and E.M. defined the project. J.R. wrote and\u0026nbsp;obtained\u0026nbsp;ethical approval for the study. E.M. collected\u0026nbsp;data on the cosmonauts. C.T. and E.A. performed\u0026nbsp;post-processing MRI\u0026nbsp;analysis. C.T. performed statistical\u0026nbsp;analysis. C.T., E.A., F.R., A.H., V.F., P.V.D.B., and J.R. contributed to\u0026nbsp;the interpretation of the results. C.T. drafted the first version of the manuscript. All the authors critically revised the manuscript and gave their approval for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCOMPETING INTERESTS DECLARATIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDATA AVAILABILITY\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on a reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eShen, M. \u0026amp; Frishman, W. H. Effects of Spaceflight on Cardiovascular Physiology and Health. 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Nat Rev Cardiol 17, 298\u0026ndash;312 (2020). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org:10.1038/s41569-019-0305-z\u003c/span\u003e\u003cspan address=\"https://doi.org:10.1038/s41569-019-0305-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"npj-microgravity","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"npjmgrav","sideBox":"Learn more about [npj Microgravity](http://www.nature.com/npjmgrav/)","snPcode":"41526","submissionUrl":"https://submission.springernature.com/new-submission/41526/3","title":"npj Microgravity","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"NPJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5010545/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5010545/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Microgravity exposure induces cardiac deconditioning, primarily due to hypovolemia and inactivity. Animal models suggest microgravity may cause left ventricular (LV) papillary muscle atrophy, but this has not been studied in humans. This study used MRI to assess LV papillary muscle mass and LV morphology and function in nine male cosmonauts before and 6 ± 2 days after long-duration spaceflight (247 ± 90 days). Spaceflight did not affect LV volumes and ejection fraction but increased heart rate (P \u003c 0.001), cardiac output (P = 0.03), and longitudinal strain parameters. There was a 13.6% decrease in LV papillary muscle mass (P = 0.017) with a trend of increase in the LV mass, increased mitral annular diameter (P = 0.004) without mitral leakage, and increased LV sphericity (P = 0.02). These findings suggest LV adapts to space with geometric changes, but microgravity-induced papillary muscle atrophy requires further study for long-term implications.","manuscriptTitle":"Long-duration Spaceflight Induces Atrophy in the Left Ventricular Papillary Muscles.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-04 13:46:58","doi":"10.21203/rs.3.rs-5010545/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-03-18T04:55:57+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-12T14:32:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"247850377020069300172246506313153932151","date":"2025-02-26T05:23:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-29T07:49:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"47664637301887365427336696405283385444","date":"2024-10-07T13:54:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3559578933881260170767613712498882227","date":"2024-10-07T04:04:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-24T04:08:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-16T06:28:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-09-06T13:24:05+00:00","index":"","fulltext":""},{"type":"submitted","content":"npj Microgravity","date":"2024-08-31T21:23:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"npj-microgravity","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"npjmgrav","sideBox":"Learn more about [npj Microgravity](http://www.nature.com/npjmgrav/)","snPcode":"41526","submissionUrl":"https://submission.springernature.com/new-submission/41526/3","title":"npj Microgravity","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"NPJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a414014e-22e8-4cd6-a57b-749015fa6b1e","owner":[],"postedDate":"October 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":38372638,"name":"Health sciences/Health care/Medical imaging/Magnetic resonance imaging"},{"id":38372639,"name":"Biological sciences/Physiology"},{"id":38372640,"name":"Health sciences/Anatomy"}],"tags":[],"updatedAt":"2025-11-17T16:02:46+00:00","versionOfRecord":{"articleIdentity":"rs-5010545","link":"https://doi.org/10.1038/s41526-025-00531-7","journal":{"identity":"npj-microgravity","isVorOnly":false,"title":"npj Microgravity"},"publishedOn":"2025-11-12 15:58:20","publishedOnDateReadable":"November 12th, 2025"},"versionCreatedAt":"2024-10-04 13:46:58","video":"","vorDoi":"10.1038/s41526-025-00531-7","vorDoiUrl":"https://doi.org/10.1038/s41526-025-00531-7","workflowStages":[]},"version":"v1","identity":"rs-5010545","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5010545","identity":"rs-5010545","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}