Validation of Noninvasive Indices of Right Ventricular Diastolic Function. Simultaneous Echocardiography and Pressure-volume Catheterization Studies

Validation of Noninvasive Indices of Right Ventricular Diastolic Function. 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Simultaneous Echocardiography and Pressure-volume Catheterization Studies Candelas Pérez del Villar, Raquel Prieto-Arévalo, Jorge García-Carreño, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6339436/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Jul, 2025 Read the published version in Cardiovascular Ultrasound → Version 1 posted 10 You are reading this latest preprint version Abstract Background The reliability of the recommended echocardiographic methods for assessing RV diastolic function has been questioned. We aimed to validate noninvasive indices of RV diastolic function, derived from tricuspid Doppler and myocardial deformation metrics, against intrinsic diastolic chamber properties and filling pressures. Methods We obtained simultaneous high-fidelity pressure-volume loops and echocardiographic data in separate animal and clinical settings: 1) a porcine model of acute hemodynamic interventions (n = 13), and 2) patients with Fallot tetralogy and pulmonary hypertension (n = 9). These designs allow for within- and between-subject validation. From the PV loops data, we obtained the reference values of RV stiffness ( S + ), elastic recoil ( S − ) and relaxation (τ) constants, as well as the contribution of passive properties to instantaneous diastolic pressures. Results In the animal setting, only the tricuspid E/A ratio and e’ velocity weakly correlated with S + (R rm :0.36 and 0.28 respectively, p < 0.01 for both). In the clinical group, no correlation was found between the echocardiographic indices and the intrinsic diastolic properties. Isovolumic relaxation time and early diastolic global strain-rate (GSR) correlated with mean right atrial pressure (RAP) (Spearman r: -0.73 and 0.85, respectively, p < 0.05 for both). E/e’ and E/GSR ratio were not associated with RAP. Tricuspid e’ and GSR negatively correlated with passive pressure component (only due to) at valve opening (R rm -0.27 and − 0.33, respectively, p < 0.01 for both). Conclusions Recommended echocardiographic indices of RV diastolic function do not reflect intrinsic RV diastolic properties. Therefore, the application of these indices for inferring RV diastolic function and filling pressures is limited. diastolic function right ventricle elastic recoil relaxation stiffness echocardiography Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Right ventricular (RV) diastolic dysfunction is a common finding in many cardiovascular diseases [ 1 ], and is a recognized determinant of symptoms and clinical outcomes in several clinical scenarios [ 2 – 5 ]. Under normal conditions, the RV works like a suction pump, providing adequate blood flow to the left heart while keeping systemic venous pressure low [ 6 ]. In the pathologies entailing overloaded RV, diastolic dysfunction results in impaired RV filling and increased right atrial pressure (RAP). Delayed myocardial relaxation,[ 7 ] increased RV chamber stiffness [ 8 ], and/or blunted elastic recoil[ 6 ] are some of the typical mechanisms of RV diastolic dysfunction. However, addressing these intrinsic diastolic chamber properties in the RV requires invasive acquisition and analysis of pressure-volume (PV) data [ 6 ]. Hence, in clinical practice, the characterization of RV diastolic function relies mostly on ultrasound. Doppler and tissue Doppler (DTI) measures of tricuspid inflow and annulus velocities are the recommended surrogates of RV diastolic properties [ 9 ], but there is growing evidence that they do not account for invasive parameters of RV diastolic function or filling pressures [ 5 , 10 – 13 ]. Conventional methods for PV data analysis have inherent limitations. For instance, when assessing the relaxation constant (τ) of the RV, traditional approaches fit the pressure-time decay during early diastole to an exponential function solely, neglecting the relative contribution of restoring forces, instrumental in RV filling [ 6 ]. Moreover, traditional methods estimate diastolic stiffness by using end-diastolic PV relationships during preload modification, assuming that relaxation has always ended. Recently, we have developed a global-optimization algorithm able to measure LV diastolic chamber properties from instantaneous pressure, time, and volume data. This approach yields a more robust assessment of diastolic chamber function than conventional window-limited methods [ 6 , 14 ]. The present study was designed to validate Doppler and strain echocardiographic indices of diastolic RV function against its intrinsic diastolic properties under different hemodynamic conditions. Methods Simultaneous echocardiographic and cardiac PV catheterization were performed in both animal and clinical experiments to account for within- and between-subject validations. (Fig. 1 ). Animal experiments We studied thirteen adult minipigs (43 ± 8 Kg, nine males) in a closed-chest instrumentation setup under anesthesia and mechanical ventilation. Anesthetic management was performed by propofol infusion (0.2 mg/Kg/min), and boluses of fentanyl (0.05 mg i.v.) and atracurium (0.3 mg/kg/h), ensuring deep anesthesia before neuromuscular blockade. A sequential protocol included in each animal: baseline (n = 13), esmolol (75–200 µg/kg/min; n = 12), dobutamine (2.5 µg/kg/min; n = 9) and acute volume overload (1,000–1,500 ml saline isotonic solution in 5–10 min; n = 9) allowing a recovering time of 20 min between interventions. Early to late endotoxic RV failure was induced by the infusion of 0.5 mg/kg of lipopolysaccharide from Escherichia coli serotype 0127:B8 (Sigma Chemical) over 30 min [ 6 , 15 ]. Early phase of endotoxic RV failure (30 min; n = 11) was characterized by acute pulmonary hypertension, whereas the late phase of endotoxic RV failure (4 hours; n = 6) entailed an overt RV failure. Animals were euthanized at the end of the experiments (pentobarbital 100 mg/kg i.v.). The experimental protocol followed the guidelines from Directive 2010/63/EU and was approved by the local Institute Animal Care Committee (ES280790000087). Through the right jugular vein, we placed a 7F pigtail PV catheter (CD-Leycom) in the RV apex connected to a dual-field conductance processor (Sigma 5DF, CD-Leycom). Additional 5F micromanometer (Millar Instruments Inc.) was positioned in the right atrium (RA). An occlusion balloon (PTS404, NuMED Inc.) was settled in the RA-inferior vena cava (IVC) junction through a femoral vein. Pressure micromanometers were carefully balanced and checked for drift. Digital signals were recorded at 1,000 Hz on a dedicated computer with custom-built amplifiers, a 16-channel analog-to-digital converter board, and virtual instrumentation software. PV data were obtained thrice during transient IVC occlusion for each hemodynamic state with the ventilation disconnected (atmospheric intrathoracic pressure) [ 6 , 15 ]. Echocardiographic images were acquired on Vivid 7 and Vivid 9 ultrasound systems (General Electric Healthcare) using broadband transducers just before PV loops acquisition. Apical views and 3D RV volumetric images were obtained through a subxifoid abdominal incision. Pulsed-wave Doppler tricuspid inflow pattern was obtained as recommended [ 9 ]. Color DTI was recorded from the apical 4-chamber. 2D apical 4-chamber view gray images were acquired at > 60 frames/s. Clinical study Two groups of patients, with indication for cardiac catheterization, were included in the clinical study: a) four patients with pulmonary hypertension (PH) and b) five patients with tetralogy of Fallot and pulmonary regurgitation. A Swan-Ganz catheter was used to measure right heart pressures and cardiac output. A high-fidelity pressure-conductance 7F pig-tail catheter (CD-Leycom) was placed in the RV apex and connected to a dual-field conductance processor (Inca, CD-Leycom). An occlusion balloon (PTS303, 30 mm, NuMED Inc.) was placed in the RA-IVC junction through a femoral vein. Pressure and conductance signals were acquired thrice during end-expiratory apnea during transient IVC occlusion after waiting for stabilization period. All signals were digitized at 250 Hz. Echocardiography images were acquired following current recommendations using the same protocol as in animal experiments [ 9 ]. All patients also underwent cardiac magnetic resonance examination (1.5 T Philips Achieva) within 24 hours obtaining cine steady-state free-precession imaging of RV function in short and axial views. Image analysis Echocardiographic images were analyzed using EchoPac (version 110.1.2, General Electric Healthcare). Peak early (E) and late (A) tricuspid inflow velocities, E/A ratio and E-wave deceleration time (DT) were measured. Color DTI was analyzed by focusing on the lateral tricuspid annulus to measure peak early (e’) and late (a’) diastolic tricuspid annular velocities and the isovolumic relaxation time (IVRT). The RV wall endocardial borders were manually traced on 2D four apical chamber views to obtain global early and late longitudinal diastolic strain rate (GSR) averaging the 6 RV segments (basal, mid, and apical of the RV free wall and septum). We also obtained E/e’ and E/early GSR ratios. RV volumes, obtained either by 3D-echocardiography (4D-RV function; TomTec Imaging Systems) (for animals) or by CMR (Medis Suite, Medis Medical Imaging Systems) (for patients), were used to calibrate the conductance signals. PV data analysis and intrinsic diastolic properties To obtain RV intrinsic diastolic properties, we used a global optimization algorithm that handles the diastolic PV data. This method has been shown to have significant advantages over conventional methodologies to analyze RV and LV PV loop data [ 6 , 14 ]. The method provides metrics of the RV intrinsic diastolic properties such as the constants of relaxation (t), elastic recoil ( S − ), and stiffness ( S + ) and allows for measuring the relative contribution of each one of these properties to the instantaneous pressure using the full diastole (from pulmonary valve closure to end-diastole) [ 6 ]. Briefly, RV diastolic pressure is modelled as the sum of relaxation–mediated pressure and the passive properties–mediated pressures. The latter is related to elastic recoil (when the RV operating volume is below the equilibrium volume - V 0 -), or to chamber stiffness (when the operating volume is above V 0 ;). Diastolic indices are calculated via global optimization. This method provides the passive pressure component of RV pressure at tricuspid valve opening (Pp at TVO) independently and separately from the relaxation component, allowing to quantify the impact of elastic recoil on RV early filling (RV suction) (Fig. 1 ) [ 6 ]. Statistical Analysis Linear mixed-effects models were used to analyze the effects of interventions on the animal data. Data are shown using least square means and standard errors, except where otherwise indicated. Differences among phases were tested using Dunnett’s contrasts against baseline measurements. Data from the clinical study are reported as median [interquartile range]. The association between echocardiographic and hemodynamic variables was assessed by within-subject correlation coefficients accounting for repeated measures (R rm ). Spearman´s rho (r) test was used to assess between-subject correlations in the clinical study. p values < 0.05 were considered significant. Statistical analysis was performed using R v.3.6.3. Results Global hemodynamics and intrinsic RV properties Interventions in animals caused a wide range of values of RV diastolic properties and load with mean RAP from − 1 to 19 mm Hg (Table 1 ). Dobutamine infusion shortened τ (29 ± 3 vs. 41 ± 3 ms at baseline, p < 0.001) whereas volume overload lengthened relaxation (τ 65 ± 3 ms, p < 0.001 vs. baseline). RV stiffening was induced by esmolol and volume infusion ( S + 14 ± 1 and 23 ± 1 mm Hg, respectively, vs. 11 ± 1 mm Hg at baseline, p < 0.05 for both). The contribution of elastic recoil to RV diastolic pressure at the onset of filling was hampered by esmolol and by early and late endotoxemia (Pp at TVO: -0.8 ± 0.4 mm Hg, -0.2 ± 0.4 mm Hg and 0.4 ± 0.5 mm Hg, respectively, p < 0.001 for all). In the clinical cohort, Fallot patients showed higher values of τ and S + than those patients with PH (Table 2 ). Table 1 Global hemodynamics and invasive pressure-volume indices of RV diastolic function in the experimental setting. Baseline Esmolol Dobutamine Volume Endotoxin early Endotoxin late Number of animals 13 12 9 9 11 6 Number of runs 47 45 32 25 39 32 Heart rate (bpm) 93 ± 3 84 ± 3* 118 ± 4* 99 ± 4 89 ± 4* 114 ± 4* Right heart pressures RV Pmax (mm Hg) 31 ± 2 30 ± 2 38 ± 2* 43 ± 2* 44 ± 2* 47 ± 2* RV Pmin (mm Hg) 0.9 ± 0.5 1.4 ± 0.5 -0.1 ± 0.5 7.7 ± 0.5* 3.4 ± 0.5* 2.2 ± 0.6 Mean RAP (mm Hg) 2.6 ± 0.7 3.3 ± 0.7 1.6 ± 0.8 10.3 ± 0.8* 5.5 ± 0.7* 2.7 ± 0.9 RVEDP (mm Hg) 5.4 ± 0.6 6.7 ± 0.6* 4.2 ± 0.7 15.0 ± 0.7* 9.2 ± 0.6* 5.8 ± 0.7 Indices of diastolic function t (ms) 41 ± 3 38 ± 3 29 ± 3* 65 ± 3* 41 ± 3 38 ± 3 S − (mm Hg) 8 ± 1 8 ± 1 5 ± 1* 11 ± 1* 9 ± 1 8 ± 1 S + (mm Hg) 11 ± 1 14s ± 1* 9 ± 1 23 ± 1* 11 ± 1 8 ± 2 Pressure decomposition at the onset of RV diastolic filling RVP at TVO (mm Hg) 3.5 ± 0.6 3.5 ± 0.7 2.2 ± 0.7* 12.6 ± 0.7* 6.7 ± 0.7* 5.2 ± 0.7* Passive pressure at TVO (mm Hg) -2.2 ± 0.4 -0.8 ± 0.4* -2.1 ± 0.4 -2.9 ± 0.5 -0.2 ± 0.4* 0.4 ± 0.5* Least square means and standard errors. *P < 0.05 vs. baseline (Dunnett’s contrasts). RV Pmax, RV maximum systolic pressure; RV Pmin, RV minimum diastolic pressure; RAP, right atrial pressure; RVEDP, RV end-diastolic pressure; 𝜏, time-constant of relaxation; S − , constant of diastolic elastic recoil; S + , constant of passive stiffness; RVP, right ventricular pressure; TVO, tricuspid valve opening. Table 2 Hemodynamic data in the patient group. Total Fallot Pulmonary Hypertension n 9 5 4 Sex (M/F) 5/4 3/2 1/3 Heart rate (bpm) 64 (61–72) 61 (56–64) 68 (63–75) Cardiac index (L/min·m2) 2.8 (2.2–3.2) 3.2 (2.8–3.5) 1.8 (1.5–2.4) Mean aortic pressure (mm Hg) 93 (80–98) 80 (67–99) 94 (90–96) Right heart and pulmonary pressures Mean RAP (mm Hg) 8 (6–11) 11 (8–12) 6 (5.5–6.5) RVEDP (mm Hg) 8 (5–11) 8 (8–11) 4.5 (3.6–7.8) RV Pmax (mm Hg) 52 (45–73) 52 (44–53) 60 (45–76) RV Pmin (mm Hg) 4.5 (1.4–5.0) 5.0 (4.6–6.7) 0.7 (-0.2–2.2) Mean PAP (mmHg) 32 (25–41) 25 (24–28) 42 (40–44) PCP (mm Hg) 10 (8–15) 15 (12–16) 6 (4–8.5) Indices of diastolic function t (ms) 55.6 (40.5–73.5) 58 (56–81) 38 (35–49) S − (mm Hg) 4.7 (0.8–5.7) 4.7 (1.0–5.7) 2.8 (0.4–8.7) S + (mm Hg) 12.6 (5.7–13.4) 13.4 (7.4–14.2) 9.1 (5.1–12.6) Pressure decomposition Passive pressure at TVO (mm Hg) 1.2 (-0.7–3.2) 2.4 (-0.7–3.2) 0.4 (-1.4–2.2) Median (interquartile range). RAP, right atrial pressure; RVEDP, RV end-diastolic pressure; RV Pmax, RV maximum systolic pressure; RV Pmin, RV minimum diastolic pressure; PAPm, mean pulmonary arterial pressure; PCP, mean pulmonary capillary pressure; 𝜏, time-constant of relaxation; S − , constant of diastolic elastic recoil; S + , constant of passive stiffness; RVP, right ventricular pressure; TVO, tricuspid valve opening. Echocardiographic indices of RV diastolic function In the animal studies, dobutamine and volume infusion increased tricuspid filling E wave velocity (49 ± 4 and 53 ± 4 cm/s, respectively, vs. 41 ± 3 cm/s at baseline) and RV early GSR (2.2 ± 0.1 and 2.3 ± 0.1 1/s, respectively, vs. 1.9 ± 0.1 1/s at baseline, p < 0.001) (Table 3 ) . Tricuspid e’ velocity also increased under dobutamine (12 ± 1 cm/s vs. 10 ± 1 cm/s at baseline, p = 0.02). Esmolol also caused a decrease in e’ wave velocity and early GSR values. Dobutamine infusion shortened the IVRT (46 ± 5 vs. 58 ± 4 ms at baseline, p = 0.007). Early doses of endotoxin infusion prolonged the IVRT (66 ± 6 ms, p < 0.001 vs. baseline), and significant increases in E/e’ and E/early GSR ratios were observed at late endotoxemia. Echocardiographic indices of RV diastolic function in patients are summarized in Table 4 . Table 3 Echocardiographic data obtained under hemodynamic interventions in pigs. Baseline Esmolol Dobutamine Volume Endotoxin early Endotoxin late Number of animals 13 12 9 9 11 6 Heart rate (bpm) 93 ± 3 84 ± 3* 118 ± 4* 99 ± 4 89 ± 4* 114 ± 4* RV Echocardiographic volumes and indices of systolic function 3D RV End-diastolic volume (ml) 47 ± 3 49 ± 3 45 ± 3 54 ± 3* 57 ± 3* 61 ± 4* 3D RV End-systolic volume (ml) 21 ± 2 24 ± 2* 18 ± 2* 25 ± 2* 29 ± 2* 38 ± 2* 3D RV ejection fraction (%) 55 ± 2 52 ± 2* 62 ± 2* 53 ± 2 49 ± 2* 40 ± 2* Cardiac output (L/min) 2.3 ± 0.1 2.1 ± 0.1* 3.1 ± 0.1* 2.8 ± 0.1* 2.5 ± 0.1 2.5 ± 0.2 Tricuspid DTI S' wave velocity (cm/s) 7 ± 0 6 ± 0* 8 ± 0* 7 ± 0 6 ± 0 6 ± 0 RV Peak Global Strain (%) -25 ± 1 -21 ± 1* -27 ± 1* -24 ± 1 -23 ± 1* -16 ± 1* RV Peak Systolic GSR (1/sec) -1.2 ± 0.0 -1.0 ± 0.0* -1.8 ± 0.0* -1.2 ± 0.0 -1.0 ± 0.0* -0.9 ± 0.0* RV Echocardiographic indices of diastolic function Tricuspid E wave velocity (cm/s) 41 ± 3 40 ± 3 49 ± 4* 53 ± 4* 45 ± 4 65 ± 4* Tricuspid A wave velocity (cm/s) 38 ± 3 29 ± 3* 47 ± 3* 51 ± 3* 37 ± 3 48 ± 5 Tricuspid E/A ratio 1.2 ± 0.1 1.5 ± 0.1* 1.1 ± 0.1 1.1 ± 0.1 1.3 ± 0.1 1.0 ± 0.2 Tricuspid E Deceleration Time (ms) 105 ± 7 106 ± 6 89 ± 7 83 ± 9* 102 ± 8 86 ± 16 Tricuspid DTI e’ wave velocity (cm/s) 10 ± 1 9 ± 1* 12 ± 1* 11 ± 1 11 ± 1 6 ± 1* Tricuspid DTI a’ wave velocity (cm/s) 10 ± 1 9 ± 1 13 ± 1* 11 ± 1* 10 ± 1 11 ± 1 E/e’ ratio 4 ± 0 5 ± 0 4 ± 1 4 ± 1 4 ± 1 17 ± 1* Tricuspid DTI IVRT (ms) 52 ± 6 51 ± 5 39 ± 6* 47 ± 6 66 ± 6* 45 ± 10 RV Early Diastolic GSR (1/sec) 1.9 ± 0.1 1.6 ± 0.1* 2.2 ± 0.1* 2.3 ± 0.1* 1.8 ± 0.1 1.2 ± 0.1* RV Late Diastolic GSR (1/sec) 1.3 ± 0.1 0.9 ± 0.1* 2.0 ± 0.1* 1.5 ± 0.1 1.0 ± 0.1* 1.3 ± 0.1 E/RV Early Diastolic GSR ratio 24 ± 2 27 ± 1 23 ± 2 26 ± 2 26 ± 2 49 ± 2* Least square means and standard errors. *p < 0.05 vs. baseline (Dunnett’s contrasts). DTI, Doppler Tissue Imaging; SR: strain rate; GSR: global strain rate; IVRT, isovolumic relaxation time; *p < 0.05 vs. Baseline. Table 4 Imaging characterization of the patient group. Total Fallot Pulmonary Hypertension n 9 5 4 RV Echocardiographic indices of diastolic function Tricuspid E wave velocity (cm/s) 41 (24–53) 53 (41–57) 24 (22–29) Tricuspid A wave velocity (cm/s) 37 (19–38) 38 (38–39) 22 (15–30) Tricuspid E/A ratio 1.4 (1.1–1.5) 1.4 (1.1–1.7) 1.4 (1.1–1.5) Tricuspid E Deceleration Time (ms) 215 (201–279) 253 (201–279) 209 (205–212) Tricuspid DTI e’ wave velocity (cm/s) 9.1 (7.6–10.4) 9.6 (7.6–10.4) 8.9 (7.8–11.8) Tricuspid DTI a’ wave velocity (cm/s) 6.9 (4.6–10.5) 3.9 (2.2–5.6) 11.3 (9.2–14.2) E/e’ ratio 4.5 (2.7–6.0) 6.0 (3.9–7.0) 3.5 (2.3–4.7) Tricuspid DTI IVRT (ms) 78 (47–97) 47 (46–60) 113 (92–133) RV Early Diastolic GSR (1/sec) 0.9 ( 0.6. − 1,2) 1.6 (1.5–1.7) 1.3 (1.0–1.3) RV Late Diastolic GSR (1/sec) 0.6 (0.4–0.8) 0.5 (0.3–0.7) 1.2 (1.1–1.4) E/RV Early Diastolic GSR ratio 38 (32–75) 34 (20–45) 27 (17–50) IVC dimension (mm) 17 (16–20) 16 (15–20) 18 (17–19) IVC collapsibility (</≥ 50%) 4/5 3/2 2/2 CMR RV volumes CMR RV End-diastolic volume (mL) 290 (148–339) 323 (297–355) 139 (118–202) CMR RV End-systolic volume (mL) 169 (76–198) 175 (170–198) 72 (61–133) CMR RV ejection fraction (%) 44 (36–48) 42 (37–46) 46 (35–50) Median (interquartile range); DTI, Doppler Tissue Imaging; SR: strain rate; GSR: global strain rate; IVRT, isovolumic relaxation time; IVC, inferior vena cava; CMR, cardiac magnetic resonance. RV echocardiography diastolic indices versus RV intrinsic diastolic properties and filling pressures Correlations between echocardiographic RV diastolic indices and intrinsic RV diastolic properties and filling pressures in the animal model and clinical cohort are shown in Table 5 , and Figs. 2 & 3 . In animals, we only found mild positive correlations of S + with the tricuspid E/A ratio (R rm 0.36, p = 0.007) and the e’ velocity (R rm 0.28, p = 0.005; Fig. 2 ). In patients, IVRT showed a strong inverse relationship with mean RAP (r= -0.73, p = 0.025) whereas RV early GSR positively correlated with RAP (r = 0.85, p = 0.004; Fig. 3 ). Neither tricuspid E/e’ nor E/RV early diastolic GSR ratio were related with mean RAP or RVEDP in the experimental or in the clinical datasets. Table 5 Relationship between diastolic echocardiographic indices with diastolic properties and filling pressures in the experimental and clinical studies. t S + S − mean RAP RVEDP Animals Pts. Animals Pts. Animals Pts. Animals Pts. Animals Pts. Tricuspid E wave velocity (cm/s) -0.03 0.5 0.02 0.53 0.10 0.43 0.22 0.54 0.15 0.38 Tricuspid E/A ratio 0.06 0.3 0.36* 0.05 0.06 -0.13 0.11 0.54 0.21 0.35 Tricuspid E Deceleration Time (ms) -0.12 0.1 0.04 -0.29 -0.14 -0.18 -0.02 -0.42 0.12 0 Tricuspid DTI e’ wave velocity (cm/s) -0.07 -0.16 0.28* -0.15 0.06 0.1 0.06 0.2 0.16 -0.27 Tricuspid E/e’ ratio 0.08 0.48 -0.21 0.38 -0.006 0.2 0.05 0.32 -0.07 0.45 Tricuspid DTI IVRT (ms) -0.04 -0.16 0.02 -0.57 -0.08 -0.1 0.06 -0.73* 0.02 -0.35 RV Global Early Diastolic SR (1/sec) -0.08 0.28 0.18 0.5 -0.08 0.45 0.08 0.85* 0.02 0.18 E/RV Early Diastolic GSR ratio 0.06 0.43 -0.14 -0.02 -0.04 -0.02 -0.09 -0.21 -0.10 0.4 Correlation coefficients for repeated measures (left) and Rho Spearman values (right) for experimental and clinical cohort (Pts). *p < 0.05. t, relaxation constant; S + , stiffness constant, S − , elastic recoil constant; RAP, right atrial pressure; RVEDP, RV end-diastolic pressure; Pts., patients; DTI, Doppler Tissue Imaging; IVRT, isovolumic relaxation time; GSR: Global Strain Rate. Pp at TVO (RV suction) positively correlated with tricuspid flow DT (R rm 0.34, p = 0.009) and was negatively related with e’ and early GSR (R rm -0.27 and − 0.33, respectively, p < 0.01 for both; Table 6 and Fig. 4 ). Table 6 Correlation between RV diastolic echocardiographic indices with passive RV pressure at early filling (suction). Passive pressure at TVO Animals Patients Tricuspid E wave velocity (cm/s) 0.06 -0.05 Tricuspid E/A ratio -0.04 0.13 Tricuspid E Deceleration Time (ms) 0.34* 0.04 Tricuspid DTI e’ wave velocity (cm/s) -0.27* -0.47 Tricuspid E/e’ ratio 0.29* 0.18 Tricuspid DTI IVRT (ms) -0.04 -0.12 RV Global Early Diastolic SR (1/sec) -0.33* -0.32 E/RV Early Diastolic GSR ratio 0.30* 0.30 Correlation coefficients for repeated measured/Rho Spearman for clinical/experimental datasets. *p < 0.05. Exp: experimental cohort; Clin: clinical cohort; RAP, right atrial pressure; TVO: tricuspid valve opening; ED: end-diastole; DTI, Doppler Tissue Imaging; IVRT, isovolumic relaxation time; GSR: Global Strain Rate Discussion To our knowledge, this is the first study aimed to validate RV echocardiographic diastolic indices, addressing within- and between- subject measurements, against ventricular relaxation and passive mechanical properties –elastic recoil and stiffness- obtained from PV loops data. By analyzing the full diastolic PV-time signals, from animal and clinical experiments, we demonstrate that neither the conventional pulsed-wave Doppler tricuspid inflow pattern, nor the tricuspid annulus DTI diastolic velocities or strain-derived measurements, properly account for the diastolic properties of the right ventricle. Our results highlight the limitations of Doppler echocardiography for inferring RV diastolic properties, and filling pressures. Determinants of echocardiographic RV diastolic indices PV loop analyses during preload modification are the gold standard to determine intrinsic ventricular diastolic chamber properties. Conventional PV data analyses have shown the limitations of Doppler echocardiography and tissue Doppler imaging to reflect intrinsic LV diastolic properties and function [ 16 ]. Similarly, the current echocardiographic recommendations for assessing RV diastolic function have been recently questioned [ 5 , 13 ]. RV filling is governed by the right atrioventricular pressure gradient, which is driven by distinct sources of forces interacting simultaneously. It is commonly accepted that, at early diastole, relaxation and elastic recoil are responsible for RV depressurization, whereas stiffness and delayed relaxation determine the end-diastolic pressure. Contrary to what happens in the LV, the isovolumic relaxation phase is often absent in the normal RV [ 1 ]. This implies volume-dependent RV passive properties may also play a major role in early RV filling. Classically, the exponential fitting of the pressure decay at early diastole (Weiss method) has been assessed RV relaxation constant (t). However, this methodology fails to discriminate the relative contribution of restoring forces to early RV depressurization [ 6 ]. Classical methods for measuring RV stiffness rely on the assumption that relaxation is completed at end-diastole [ 8 ]. However, it is known that in chronic overloaded RVs, chamber filling is often impaired by shorter diastolic times [ 17 ]. Thus, prolonged τ leads to incomplete relaxation, and larger end-diastolic pressures [ 7 ]. This emphasizes the need for an intrinsic stiffness parameter, independent of residual relaxation. In this work, we overcome these limitations by using a method capable of decoupling ventricular relaxation and passive mechanical properties [ 6 , 14 ]. Previous studies using conventional relaxation analyses have shown a direct relationship between τ and E wave DT [ 10 , 18 ]. However, as mentioned above, prolonged t obtained using the Weiss method may induce to misinterpretation. In fact, when we calculated the RV pressure diastolic components separately, we observed a negative moderate correlation between passive RV suction and E wave DT (Table 6 ). Mitral e’ has shown to be dependent on relaxation rate and restoring forces, and it is inversely related to passive stiffness [ 19 ]. In our experimental study, we observed a mild positive correlation between stiffness ( S + ) and RV passive suction (Table 6 and Fig. 4 ). This suggests stiffer RVs present higher tricuspid velocities, highlighting the stiffness contribution to early RV filling. Limitations of echocardiography to assess right filling pressures Noninvasive estimation of filling pressures is one of the main objectives of the echocardiographic assessment of diastolic function. In the right heart, an elevated RAP is the earliest sign of a failing ventricle and determines symptoms and prognosis of many cardiovascular diseases [ 2 , 4 ]. Besides the diameter of the inferior vena cava and the right atrium size, tricuspid E/A and E/e’ ratios are recommended indices to infer RV filling pressures [ 9 ]. Those recommendations are based on the hypotheses that early filling depends only on the effects of atrial pressure and the degree of the chamber depressurization, assuming a reduced early diastolic annular velocity when relaxation is impaired. Hence, eGSR has been proposed to account for right ventricular relaxation, and the E/eGSR ratio suggested to reflect RV filling pressures [ 11 , 18 ]. However, we did not find Doppler, DTI or myocardial deformation indices to be related with elevated mean RAP in a controlled experimental setting. Specifically, in the group of patients, IVRT negatively correlated with mean RAP, whereas it positively correlated with RV eGSR. These observations deserve further exploration in larger sets of patients. Clinical implications Although, the tricuspid inflow pattern and the E/e’ ratio are included in the current echocardiographic recommendations for assessing RV diastolic function [ 9 ], there is increasing evidence that calls it into question [ 5 , 13 ]. Tricuspid filling and DTI parameters may be useful in some scenarios, as in the overloaded RV, to approximate filling pressures, and may provide prognosis information in the overloaded RV [ 20 ]. However, our results highlight their limitations. In this work, we demonstrate that some of the conventional and myocardial deformation indices are unable to reflect the impact of different hemodynamic conditions on the intrinsic diastolic properties and filling pressures of the RV. Moreover, our work shows traditional noninvasive indices do not reflect therapeutic changes in RV pathologies. Multi-parametrical algorithms, combining several Doppler and morphological parameters —as currently recommended to evaluate LV diastolic function and filling pressures- [ 21 ] should be specifically validated for the RV. Limitations We acknowledge the number of studied patients is small. However, we believe our results, combining clinical and experimental models, provide sufficient evidence to serve as a proof of concept for future studies. Animal studies of acute RV modulation may not be extensible to chronic scenarios of RV overload and were performed under general anesthesia, which may explain the differences between the clinical and animal datasets. Late phase of endotoxemia is characterized by a systemic inflammatory syndrome, similar to sepsis. This may explain the low mean RAP observed during those phases, despite the presence of RV dysfunction. Some echocardiographic parameters related to RV diastolic function and mean RAP, such as right atrial size and deformation, suprahepatic flow pattern, or combined parameters of the above [ 5 ], were not analyzed. Of note, intraventricular fluid dynamics play an important role in the filling of normal and remodeled LVs [ 22 ]. However, its impact on the RV filling has not been addressed. Conclusions Currently recommended Doppler, DTI and strain-based ultrasound indices of RV diastolic function weakly account for the intrinsic RV chamber diastolic properties. These findings suggest that current recommendations for the assessment of RV diastolic function and filling pressures in the clinical setting should be revisited. Abbreviations DTI Doppler tissue imaging GSR Early global longitudinal diastolic strain-rate IVC Inferior vena cava IVRT Isovolumetric relaxation time PV Pressure-volume RAP Right atrial pressure Declarations Ethics approval and consent to participate The clinical study protocol complied with the Declaration of Helsinki and was approved by the Committee on Ethics in Drug Research of the Gregorio Marañón Health Research Institute (282/12 and 335/16). All patients provided written informed consent to participate in the study. Availability of data and materials The data underlying this article will be shared on request to the corresponding author. Competing interests The authors declare no competing interests. Funding Sources This work was supported by grants PI12/02885 (to JB); CM12/00273 and JR15/00039 (to CPV); and PI16/01237 (to CPV and RP-A) from the Instituto de Salud Carlos III and by the EU – European Regional Development Fund. CPV was also funded by Gerencia Regional de Salud de Castilla y León (INT/M/10/23). Authors' contributions C.P.d.V., R.P.A. and J.B. conception and design of research; C.P.d.V., R.P.A., D.R.-P., P.M.-L., Y.B., M.M.D., A.D.M., R.C.B. and J.C.A. performed experiments; C.P.d.V., R.P.A., P.M.-L., Y.B., A.D.M., C.H.F. and R.C.B. analyzed data; C.P.d.V., R.P.A., P.M.-L and J.B. interpreted results of experiments; C.P.d.V. and P.M.-L. prepared figures; C.P.d.V., R.P.A. and P.M-L drafted manuscript; J.B., C.P.d.V., R.P.A., P.M.-L., D.R.-P, Y.B., A.D.M., C.H.F., R.C.B., J.B. and F.F.A edited and revised manuscript; all authors approved final version of manuscript. Acknowledgements Not applicable. References Haddad F, Doyle R, Murphy DJ, Hunt SA. Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical importance, and management of right ventricular failure. Circulation. 2008;117(13):1717–31. Weatherald J, Boucly A, Chemla D, Savale L, Peng M, Jevnikar M, et al. Prognostic Value of Follow-Up Hemodynamic Variables After Initial Management in Pulmonary Arterial Hypertension. Circulation. 2018;137(7):693–704. Rommel KP, von Roeder M, Oberueck C, Latuscynski K, Besler C, Blazek S, et al. Load-Independent Systolic and Diastolic Right Ventricular Function in Heart Failure With Preserved Ejection Fraction as Assessed by Resting and Handgrip Exercise Pressure-Volume Loops. Circ Heart Fail. 2018;11(2):e004121. Egbe AC, Pellikka PA, Miranda WR, Bonnichsen C, Reddy YNV, Borlaug BA, et al. Echocardiographic predictors of severe right ventricular diastolic dysfunction in tetralogy of Fallot: Relations to patient outcomes. Int J Cardiol. 2020;306:49–55. Yogeswaran A, Rako ZA, Yildiz S, Ghofrani HA, Seeger W et al. Brito da Rocha B,. Echocardiographic evaluation of right ventricular diastolic function in pulmonary hypertension. ERJ Open Res. 2023;9(5). Del Perez C, Bermejo J, Rodriguez-Perez D, Martinez-Legazpi P, Benito Y, Antoranz JC, et al. The role of elastic restoring forces in right-ventricular filling. Cardiovasc Res. 2015;107(1):45–55. McCabe C, White PA, Hoole SP, Axell RG, Priest AN, Gopalan D, et al. Right ventricular dysfunction in chronic thromboembolic obstruction of the pulmonary artery: a pressure-volume study using the conductance catheter. J Appl Physiol. 2014;116(4):355–63. Rain S, Handoko ML, Trip P, Gan CT, Westerhof N, Stienen GJ, et al. Right ventricular diastolic impairment in patients with pulmonary arterial hypertension. Circulation. 2013;128(18):2016. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685–713. quiz 86 – 8. Okumura K, Slorach C, Mroczek D, Dragulescu A, Mertens L, Redington AN, et al. Right ventricular diastolic performance in children with pulmonary arterial hypertension associated with congenital heart disease: correlation of echocardiographic parameters with invasive reference standards by high-fidelity micromanometer catheter. Circ Cardiovasc Imaging. 2014;7(3):491–501. Moriyama H, Murata M, Tsugu T, Kawakami T, Kataoka M, Hiraide T, et al. The clinical value of assessing right ventricular diastolic function after balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension. 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Yotti R, Bermejo J, Benito Y, Antoranz JC, Desco MM, Rodriguez-Perez D, et al. Noninvasive estimation of the rate of relaxation by the analysis of intraventricular pressure gradients. Circ Cardiovasc Imaging. 2011;4(2):94–104. Alkon J, Humpl T, Manlhiot C, McCrindle BW, Reyes JT, Friedberg MK. Usefulness of the right ventricular systolic to diastolic duration ratio to predict functional capacity and survival in children with pulmonary arterial hypertension. Am J Cardiol. 2010;106(3):430–6. Chowdhury SM, Goudar SP, Baker GH, Taylor CL, Shirali GS, Friedberg MK, et al. Speckle-Tracking Echocardiographic Measures of Right Ventricular Diastolic Function Correlate with Reference Standard Measures Before and After Preload Alteration in Children. Pediatr Cardiol. 2017;38(1):27–35. Kasner M, Westermann D, Steendijk P, Gaub R, Wilkenshoff U, Weitmann K, et al. Utility of Doppler echocardiography and tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction: a comparative Doppler-conductance catheterization study. Circulation. 2007;116(6):637–47. Pagourelias ED, Efthimiadis GK, Parcharidou DG, Gossios TD, Kamperidis V, Karoulas T, et al. Prognostic value of right ventricular diastolic function indices in hypertrophic cardiomyopathy. Eur J Echocardiogr. 2011;12(11):809–17. Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, et al. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016;29(4):277–314. Martinez-Legazpi P, Bermejo J, Benito Y, Yotti R, Del Perez C, Gonzalez-Mansilla A, et al. Contribution of the diastolic vortex ring to left ventricular filling. J Am Coll Cardiol. 2014;64(16):1711–21. Additional Declarations No competing interests reported. Supplementary Files floatimage1.jpeg Cite Share Download PDF Status: Published Journal Publication published 09 Jul, 2025 Read the published version in Cardiovascular Ultrasound → Version 1 posted Editorial decision: Revision requested 29 Apr, 2025 Reviews received at journal 24 Apr, 2025 Reviews received at journal 24 Apr, 2025 Reviewers agreed at journal 20 Apr, 2025 Reviewers agreed at journal 14 Apr, 2025 Reviewers agreed at journal 07 Apr, 2025 Reviewers invited by journal 07 Apr, 2025 Editor assigned by journal 02 Apr, 2025 Submission checks completed at journal 02 Apr, 2025 First submitted to journal 30 Mar, 2025 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. 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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-6339436","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":439576395,"identity":"d1c53e08-c888-40f9-8ccb-3e4fcb9452fa","order_by":0,"name":"Candelas Pérez del Villar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/klEQVRIie2QsWoCQRCGZ1lYm0PbrfQVVq70ZeYQcs2FBNKkkHgSuEpSR/IS+gYjC2cTuNYiyIW8wEJAUhziaBqLbLS02K+bZT/++QcgELheJLRBTKgG6PIk6CJFgcgJAeLDeKnCP1lJ8nNK5+25dK4ZdJUecspok84rWxM8PnkV/VEOZ69RGiudsFI+3M7XN4bg3XoVo7NYRtomRbRkRSErYEgU/t2MvvuWjbHjX2WHqalWjsTOvxinSAloUbUmOSUFoqGMU3L5X5dYTCntF0flBfuzdXbPpfxd+GJf8NMMeh3Z+qzdFnvtarWo3ci/GOg/X9Ev+JRAIBAInLAHUTBdY4ZZ/a8AAAAASUVORK5CYII=","orcid":"","institution":"Complejo Asistencial Universitario de Salamanca, Spain","correspondingAuthor":true,"prefix":"","firstName":"Candelas","middleName":"Pérez del","lastName":"Villar","suffix":""},{"id":439576399,"identity":"8d7bc1de-3e8e-4348-a369-48ceca2cee67","order_by":1,"name":"Raquel Prieto-Arévalo","email":"","orcid":"","institution":"Hospital General Universitario Gregorio Marañón","correspondingAuthor":false,"prefix":"","firstName":"Raquel","middleName":"","lastName":"Prieto-Arévalo","suffix":""},{"id":439576400,"identity":"0b00e20c-c21f-4237-ac5b-c8dc9f8d947a","order_by":2,"name":"Jorge García-Carreño","email":"","orcid":"","institution":"Hospital General Universitario Gregorio Marañón","correspondingAuthor":false,"prefix":"","firstName":"Jorge","middleName":"","lastName":"García-Carreño","suffix":""},{"id":439576401,"identity":"fb72f457-cf69-49da-bca9-c5ce6c95870a","order_by":3,"name":"Pablo Martínez-Legazpi","email":"","orcid":"","institution":"Universidad Nacional de Educación a Distancia","correspondingAuthor":false,"prefix":"","firstName":"Pablo","middleName":"","lastName":"Martínez-Legazpi","suffix":""},{"id":439576402,"identity":"4ab8a7b6-80bd-480c-9c82-124383a53650","order_by":4,"name":"Daniel Rodríguez-Pérez","email":"","orcid":"","institution":"Universidad Nacional de Educación a Distancia","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Rodríguez-Pérez","suffix":""},{"id":439576403,"identity":"a53343c3-5aa2-4bc8-b673-da4e4d412e4e","order_by":5,"name":"Yolanda Benito","email":"","orcid":"","institution":"Hospital General Universitario Gregorio Marañón","correspondingAuthor":false,"prefix":"","firstName":"Yolanda","middleName":"","lastName":"Benito","suffix":""},{"id":439576404,"identity":"34878d8d-efdc-4351-8afa-32c6a1baa34d","order_by":6,"name":"Antonia Delgado-Montero","email":"","orcid":"","institution":"Hospital General Universitario Gregorio Marañón","correspondingAuthor":false,"prefix":"","firstName":"Antonia","middleName":"","lastName":"Delgado-Montero","suffix":""},{"id":439576405,"identity":"6db736b9-5b6d-4a9e-85fc-3ecffffcdb0c","order_by":7,"name":"J. 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Mar Desco","email":"","orcid":"","institution":"Universidad Nacional de Educación a Distancia","correspondingAuthor":false,"prefix":"","firstName":"M.","middleName":"Mar","lastName":"Desco","suffix":""},{"id":439576408,"identity":"92a5b6c5-2791-4124-bd2f-acfd9fd49802","order_by":9,"name":"Cristian Herrera Flores","email":"","orcid":"","institution":"Complejo Asistencial Universitario de Salamanca, Spain","correspondingAuthor":false,"prefix":"","firstName":"Cristian","middleName":"Herrera","lastName":"Flores","suffix":""},{"id":439576410,"identity":"cfb3f33e-7fba-436a-9702-8666fc0548e9","order_by":10,"name":"Rafael Corisco-Beltrán","email":"","orcid":"","institution":"Hospital General Universitario Gregorio Marañón","correspondingAuthor":false,"prefix":"","firstName":"Rafael","middleName":"","lastName":"Corisco-Beltrán","suffix":""},{"id":439576413,"identity":"61ab4602-1d16-47a9-869b-e8983bf63965","order_by":11,"name":"Francisco Fernández-Avilés","email":"","orcid":"","institution":"Hospital General Universitario Gregorio Marañón","correspondingAuthor":false,"prefix":"","firstName":"Francisco","middleName":"","lastName":"Fernández-Avilés","suffix":""},{"id":439576416,"identity":"d4475a2e-34a7-477d-a3a2-325fc4e00b4e","order_by":12,"name":"Javier Bermejo","email":"","orcid":"","institution":"Hospital General Universitario Gregorio Marañón","correspondingAuthor":false,"prefix":"","firstName":"Javier","middleName":"","lastName":"Bermejo","suffix":""}],"badges":[],"createdAt":"2025-03-30 16:08:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6339436/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6339436/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12947-025-00351-5","type":"published","date":"2025-07-09T15:57:15+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":80294231,"identity":"7fe82214-d17e-45bd-a52d-a82c11d2aeeb","added_by":"auto","created_at":"2025-04-10 08:24:03","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":649124,"visible":true,"origin":"","legend":"\u003cp\u003eExperimental (left) and clinical (right) studies protocols.\u003cem\u003e Left Bottom: \u003c/em\u003eIntrinsic properties, example of RV pressure-volume (PV) loops acquired during inferior vena cava occlusion and an example of active and passive pressure decoupling. \u0026nbsp;is the net sum of active (P\u003csub\u003ea\u003c/sub\u003e) and passive (P\u003csub\u003ep\u003c/sub\u003e) components, V\u003csub\u003e0\u003c/sub\u003e: the equilibrium volume and TVO: the instant of tricuspid valve opening. \u003cem\u003eRight Bottom: \u003c/em\u003eEchocardiographic imaging acquisition protocol: Tricuspid pulsed-Doppler inflow spectrogram (panel A), tricuspid annulus color Doppler tissular imaging (DTI) (panel B), RV speckle tracking deformation analysis (panel D-E) and RV 3D echocardiography and volumetric analysis (panel C and F).\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6339436/v1/9e6f32cb4b15d6e6fe7d4277.jpeg"},{"id":80291952,"identity":"eb2dcad2-49af-48ff-b41e-4e21add0a61d","added_by":"auto","created_at":"2025-04-10 08:08:03","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":651936,"visible":true,"origin":"","legend":"\u003cp\u003eScatterplots of stiffness (\u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sub\u003e) constant \u003cem\u003evs.\u003c/em\u003e tricuspid e’ velocity (panel A) and mean right atrial pressure \u003cem\u003evs.\u003c/em\u003e E/e’ (panel B) in the experimental dataset\u003cem\u003e. \u003c/em\u003eData from each animal are plotted individually for each phase. Global (dashed line) and individual (solid line) mixed model linear fittings are superimposed.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6339436/v1/10a32f890602ba0a3660d11f.jpeg"},{"id":80293265,"identity":"eb272cb1-aab5-4a8d-8944-8161aca7d35c","added_by":"auto","created_at":"2025-04-10 08:16:03","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":551649,"visible":true,"origin":"","legend":"\u003cp\u003eRelationship between intrinsic diastolic properties (relaxation -t- and stiffness -\u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sub\u003e; panel A and B) and mean right atrial pressure (RAP; panel C and D) and echocardiography diastolic indices in the clinical dataset. Mean individual values with the regression solid line are plotted. The dotted ellipse represents the 95% confidence level for a t-distribution.\u003c/p\u003e","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6339436/v1/17c9c87bfa69741eae98c4be.jpeg"},{"id":80291962,"identity":"b6ce6776-5274-4ea5-a181-44eaa8ff9332","added_by":"auto","created_at":"2025-04-10 08:08:03","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":628626,"visible":true,"origin":"","legend":"\u003cp\u003eScatterplot of e’ velocity \u003cem\u003evs.\u003c/em\u003ethe passive pressure component at tricuspid valve opening in experimental dataset. Data from each animal are plotted individually for each phase. Global (dashed line) and individual (solid line) mixed model linear regressions are superimposed.\u003c/p\u003e","description":"","filename":"floatimage8.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6339436/v1/8a67adfa527936dd124adc2d.jpeg"},{"id":86699347,"identity":"b176d10f-087d-4035-ac1d-f11af241fb1d","added_by":"auto","created_at":"2025-07-14 16:08:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4156983,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6339436/v1/3c6fc9da-8074-4540-931a-58ea26f43f53.pdf"},{"id":80291955,"identity":"ecd85ba3-4083-4042-b07b-3c5e42190f58","added_by":"auto","created_at":"2025-04-10 08:08:03","extension":"jpeg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":999441,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6339436/v1/4d41f86bb2e319afe053aac3.jpeg"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eValidation of Noninvasive Indices of Right Ventricular Diastolic Function. Simultaneous Echocardiography and Pressure-volume Catheterization Studies\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eRight ventricular (RV) diastolic dysfunction is a common finding in many cardiovascular diseases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], and is a recognized determinant of symptoms and clinical outcomes in several clinical scenarios [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Under normal conditions, the RV works like a suction pump, providing adequate blood flow to the left heart while keeping systemic venous pressure low [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the pathologies entailing overloaded RV, diastolic dysfunction results in impaired RV filling and increased right atrial pressure (RAP). Delayed myocardial relaxation,[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] increased RV chamber stiffness [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], and/or blunted elastic recoil[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] are some of the typical mechanisms of RV diastolic dysfunction. However, addressing these intrinsic diastolic chamber properties in the RV requires invasive acquisition and analysis of pressure-volume (PV) data [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Hence, in clinical practice, the characterization of RV diastolic function relies mostly on ultrasound.\u003c/p\u003e \u003cp\u003eDoppler and tissue Doppler (DTI) measures of tricuspid inflow and annulus velocities are the recommended surrogates of RV diastolic properties [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], but there is growing evidence that they do not account for invasive parameters of RV diastolic function or filling pressures [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConventional methods for PV data analysis have inherent limitations. For instance, when assessing the relaxation constant (τ) of the RV, traditional approaches fit the pressure-time decay during early diastole to an exponential function solely, neglecting the relative contribution of restoring forces, instrumental in RV filling [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Moreover, traditional methods estimate diastolic stiffness by using end-diastolic PV relationships during preload modification, assuming that relaxation has always ended. Recently, we have developed a global-optimization algorithm able to measure LV diastolic chamber properties from instantaneous pressure, time, and volume data. This approach yields a more robust assessment of diastolic chamber function than conventional window-limited methods [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe present study was designed to validate Doppler and strain echocardiographic indices of diastolic RV function against its intrinsic diastolic properties under different hemodynamic conditions.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eSimultaneous echocardiographic and cardiac PV catheterization were performed in both animal and clinical experiments to account for within- and between-subject validations. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eAnimal experiments\u003c/h2\u003e \u003cp\u003eWe studied thirteen adult minipigs (43\u0026thinsp;\u0026plusmn;\u0026thinsp;8 Kg, nine males) in a closed-chest instrumentation setup under anesthesia and mechanical ventilation. Anesthetic management was performed by propofol infusion (0.2 mg/Kg/min), and boluses of fentanyl (0.05 mg i.v.) and atracurium (0.3 mg/kg/h), ensuring deep anesthesia before neuromuscular blockade. A sequential protocol included in each animal: baseline (n\u0026thinsp;=\u0026thinsp;13), esmolol (75\u0026ndash;200 \u0026micro;g/kg/min; n\u0026thinsp;=\u0026thinsp;12), dobutamine (2.5 \u0026micro;g/kg/min; n\u0026thinsp;=\u0026thinsp;9) and acute volume overload (1,000\u0026ndash;1,500 ml saline isotonic solution in 5\u0026ndash;10 min; n\u0026thinsp;=\u0026thinsp;9) allowing a recovering time of 20 min between interventions. Early to late endotoxic RV failure was induced by the infusion of 0.5 mg/kg of lipopolysaccharide from \u003cem\u003eEscherichia coli\u003c/em\u003e serotype 0127:B8 (Sigma Chemical) over 30 min [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Early phase of endotoxic RV failure (30 min; n\u0026thinsp;=\u0026thinsp;11) was characterized by acute pulmonary hypertension, whereas the late phase of endotoxic RV failure (4 hours; n\u0026thinsp;=\u0026thinsp;6) entailed an overt RV failure. Animals were euthanized at the end of the experiments (pentobarbital 100 mg/kg i.v.). The experimental protocol followed the guidelines from Directive 2010/63/EU and was approved by the local Institute Animal Care Committee (ES280790000087).\u003c/p\u003e \u003cp\u003eThrough the right jugular vein, we placed a 7F pigtail PV catheter (CD-Leycom) in the RV apex connected to a dual-field conductance processor (Sigma 5DF, CD-Leycom). Additional 5F micromanometer (Millar Instruments Inc.) was positioned in the right atrium (RA). An occlusion balloon (PTS404, NuMED Inc.) was settled in the RA-inferior vena cava (IVC) junction through a femoral vein. Pressure micromanometers were carefully balanced and checked for drift. Digital signals were recorded at 1,000 Hz on a dedicated computer with custom-built amplifiers, a 16-channel analog-to-digital converter board, and virtual instrumentation software. PV data were obtained thrice during transient IVC occlusion for each hemodynamic state with the ventilation disconnected (atmospheric intrathoracic pressure) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEchocardiographic images were acquired on Vivid 7 and Vivid 9 ultrasound systems (General Electric Healthcare) using broadband transducers just before PV loops acquisition. Apical views and 3D RV volumetric images were obtained through a subxifoid abdominal incision. Pulsed-wave Doppler tricuspid inflow pattern was obtained as recommended [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Color DTI was recorded from the apical 4-chamber. 2D apical 4-chamber view gray images were acquired at \u0026gt;\u0026thinsp;60 frames/s.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eClinical study\u003c/h3\u003e\n\u003cp\u003eTwo groups of patients, with indication for cardiac catheterization, were included in the clinical study: a) four patients with pulmonary hypertension (PH) and b) five patients with tetralogy of Fallot and pulmonary regurgitation.\u003c/p\u003e \u003cp\u003eA Swan-Ganz catheter was used to measure right heart pressures and cardiac output. A high-fidelity pressure-conductance 7F pig-tail catheter (CD-Leycom) was placed in the RV apex and connected to a dual-field conductance processor (Inca, CD-Leycom). An occlusion balloon (PTS303, 30 mm, NuMED Inc.) was placed in the RA-IVC junction through a femoral vein. Pressure and conductance signals were acquired thrice during end-expiratory apnea during transient IVC occlusion after waiting for stabilization period. All signals were digitized at 250 Hz. Echocardiography images were acquired following current recommendations using the same protocol as in animal experiments [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. All patients also underwent cardiac magnetic resonance examination (1.5 T Philips Achieva) within 24 hours obtaining cine steady-state free-precession imaging of RV function in short and axial views.\u003c/p\u003e\n\u003ch3\u003eImage analysis\u003c/h3\u003e\n\u003cp\u003eEchocardiographic images were analyzed using EchoPac (version 110.1.2, General Electric Healthcare). Peak early (E) and late (A) tricuspid inflow velocities, E/A ratio and E-wave deceleration time (DT) were measured. Color DTI was analyzed by focusing on the lateral tricuspid annulus to measure peak early (e\u0026rsquo;) and late (a\u0026rsquo;) diastolic tricuspid annular velocities and the isovolumic relaxation time (IVRT). The RV wall endocardial borders were manually traced on 2D four apical chamber views to obtain global early and late longitudinal diastolic strain rate (GSR) averaging the 6 RV segments (basal, mid, and apical of the RV free wall and septum). We also obtained E/e\u0026rsquo; and E/early GSR ratios. RV volumes, obtained either by 3D-echocardiography (4D-RV function; TomTec Imaging Systems) (for animals) or by CMR (Medis Suite, Medis Medical Imaging Systems) (for patients), were used to calibrate the conductance signals.\u003c/p\u003e\n\u003ch3\u003ePV data analysis and intrinsic diastolic properties\u003c/h3\u003e\n\u003cp\u003eTo obtain RV intrinsic diastolic properties, we used a global optimization algorithm that handles the diastolic PV data. This method has been shown to have significant advantages over conventional methodologies to analyze RV and LV PV loop data [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The method provides metrics of the RV intrinsic diastolic properties such as the constants of relaxation (t), elastic recoil (\u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e\u0026minus;\u003c/em\u003e\u003c/sub\u003e), and stiffness (\u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sub\u003e) and allows for measuring the relative contribution of each one of these properties to the instantaneous pressure using the full diastole (from pulmonary valve closure to end-diastole) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Briefly, RV diastolic pressure is modelled as the sum of relaxation\u0026ndash;mediated pressure and the passive properties\u0026ndash;mediated pressures. The latter is related to elastic recoil (when the RV operating volume is below the equilibrium volume -\u003cem\u003eV\u003c/em\u003e\u003csub\u003e\u003cem\u003e0\u003c/em\u003e\u003c/sub\u003e-), or to chamber stiffness (when the operating volume is above \u003cem\u003eV\u003c/em\u003e\u003csub\u003e\u003cem\u003e0\u003c/em\u003e\u003c/sub\u003e;). Diastolic indices are calculated via global optimization. This method provides the passive pressure component of RV pressure at tricuspid valve opening (Pp at TVO) independently and separately from the relaxation component, allowing to quantify the impact of elastic recoil on RV early filling (RV suction) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eLinear mixed-effects models were used to analyze the effects of interventions on the animal data. Data are shown using least square means and standard errors, except where otherwise indicated. Differences among phases were tested using Dunnett\u0026rsquo;s contrasts against baseline measurements. Data from the clinical study are reported as median [interquartile range]. The association between echocardiographic and hemodynamic variables was assessed by within-subject correlation coefficients accounting for repeated measures (R\u003csub\u003erm\u003c/sub\u003e). Spearman\u0026acute;s rho (r) test was used to assess between-subject correlations in the clinical study. \u003cem\u003ep\u003c/em\u003e values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered significant. Statistical analysis was performed using R v.3.6.3.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eGlobal hemodynamics and intrinsic RV properties\u003c/h2\u003e \u003cp\u003eInterventions in animals caused a wide range of values of RV diastolic properties and load with mean RAP from \u0026minus;\u0026thinsp;1 to 19 mm Hg (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Dobutamine infusion shortened τ (29\u0026thinsp;\u0026plusmn;\u0026thinsp;3 \u003cem\u003evs.\u003c/em\u003e 41\u0026thinsp;\u0026plusmn;\u0026thinsp;3 ms at baseline, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) whereas volume overload lengthened relaxation (τ 65\u0026thinsp;\u0026plusmn;\u0026thinsp;3 ms, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 \u003cem\u003evs.\u003c/em\u003e baseline). RV stiffening was induced by esmolol and volume infusion (\u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sub\u003e 14\u0026thinsp;\u0026plusmn;\u0026thinsp;1 and 23\u0026thinsp;\u0026plusmn;\u0026thinsp;1 mm Hg, respectively, \u003cem\u003evs.\u003c/em\u003e 11\u0026thinsp;\u0026plusmn;\u0026thinsp;1 mm Hg at baseline, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 for both). The contribution of elastic recoil to RV diastolic pressure at the onset of filling was hampered by esmolol and by early and late endotoxemia (Pp at TVO: -0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 mm Hg, -0.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 mm Hg and 0.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 mm Hg, respectively, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all). In the clinical cohort, Fallot patients showed higher values of τ and S\u003csub\u003e+\u003c/sub\u003e than those patients with PH (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\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\u003eGlobal hemodynamics and invasive pressure-volume indices of RV diastolic function in the experimental setting.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEsmolol\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDobutamine\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVolume\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEndotoxin early\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEndotoxin late\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of animals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of runs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart rate (bpm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84\u0026thinsp;\u0026plusmn;\u0026thinsp;3*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e118\u0026thinsp;\u0026plusmn;\u0026thinsp;4*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e99\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e89\u0026thinsp;\u0026plusmn;\u0026thinsp;4*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e114\u0026thinsp;\u0026plusmn;\u0026thinsp;4*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRight heart pressures\u003c/b\u003e\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRV Pmax (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38\u0026thinsp;\u0026plusmn;\u0026thinsp;2*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43\u0026thinsp;\u0026plusmn;\u0026thinsp;2*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e44\u0026thinsp;\u0026plusmn;\u0026thinsp;2*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e47\u0026thinsp;\u0026plusmn;\u0026thinsp;2*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRV Pmin (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean RAP (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRVEDP (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIndices of diastolic function\u003c/b\u003e\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003et (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29\u0026thinsp;\u0026plusmn;\u0026thinsp;3*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65\u0026thinsp;\u0026plusmn;\u0026thinsp;3*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e41\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e38\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e\u0026minus;\u003c/em\u003e\u003c/sub\u003e (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u0026thinsp;\u0026plusmn;\u0026thinsp;1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11\u0026thinsp;\u0026plusmn;\u0026thinsp;1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sub\u003e (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14s\u0026thinsp;\u0026plusmn;\u0026thinsp;1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23\u0026thinsp;\u0026plusmn;\u0026thinsp;1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePressure decomposition at the onset of RV diastolic filling\u003c/b\u003e\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRVP at TVO (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePassive pressure at TVO (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eLeast square means and standard errors. *P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs. baseline (Dunnett\u0026rsquo;s contrasts). RV Pmax, RV maximum systolic pressure; RV Pmin, RV minimum diastolic pressure; RAP, right atrial pressure; RVEDP, RV end-diastolic pressure; \u0026#120591;, time-constant of relaxation; \u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e\u0026minus;\u003c/em\u003e\u003c/sub\u003e, constant of diastolic elastic recoil; \u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sub\u003e, constant of passive stiffness; RVP, right ventricular pressure; TVO, tricuspid valve opening.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\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\u003eHemodynamic data in the patient group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFallot\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePulmonary Hypertension\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (M/F)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1/3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart rate (bpm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (61\u0026ndash;72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 (56\u0026ndash;64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68 (63\u0026ndash;75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac index (L/min\u0026middot;m2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.8 (2.2\u0026ndash;3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2 (2.8\u0026ndash;3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.8 (1.5\u0026ndash;2.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean aortic pressure (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93 (80\u0026ndash;98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 (67\u0026ndash;99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94 (90\u0026ndash;96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRight heart and pulmonary pressures\u003c/b\u003e\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean RAP (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (6\u0026ndash;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (8\u0026ndash;12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (5.5\u0026ndash;6.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRVEDP (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (5\u0026ndash;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (8\u0026ndash;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.5 (3.6\u0026ndash;7.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRV Pmax (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (45\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (44\u0026ndash;53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 (45\u0026ndash;76)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRV Pmin (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5 (1.4\u0026ndash;5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.0 (4.6\u0026ndash;6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7 (-0.2\u0026ndash;2.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean PAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (25\u0026ndash;41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (24\u0026ndash;28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (40\u0026ndash;44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCP (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (8\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (12\u0026ndash;16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (4\u0026ndash;8.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIndices of diastolic function\u003c/b\u003e\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003et (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.6 (40.5\u0026ndash;73.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58 (56\u0026ndash;81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38 (35\u0026ndash;49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e\u0026minus;\u003c/em\u003e\u003c/sub\u003e (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.7 (0.8\u0026ndash;5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.7 (1.0\u0026ndash;5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.8 (0.4\u0026ndash;8.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sub\u003e (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.6 (5.7\u0026ndash;13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.4 (7.4\u0026ndash;14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.1 (5.1\u0026ndash;12.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePressure decomposition\u003c/b\u003e\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePassive pressure at TVO (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.2 (-0.7\u0026ndash;3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.4 (-0.7\u0026ndash;3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.4 (-1.4\u0026ndash;2.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eMedian (interquartile range). RAP, right atrial pressure; RVEDP, RV end-diastolic pressure; RV Pmax, RV maximum systolic pressure; RV Pmin, RV minimum diastolic pressure; PAPm, mean pulmonary arterial pressure; PCP, mean pulmonary capillary pressure; \u0026#120591;, time-constant of relaxation; \u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e\u0026minus;\u003c/em\u003e\u003c/sub\u003e, constant of diastolic elastic recoil; \u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sub\u003e, constant of passive stiffness; RVP, right ventricular pressure; TVO, tricuspid valve opening.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEchocardiographic indices of RV diastolic function\u003c/h3\u003e\n\u003cp\u003eIn the animal studies, dobutamine and volume infusion increased tricuspid filling E wave velocity (49\u0026thinsp;\u0026plusmn;\u0026thinsp;4 and 53\u0026thinsp;\u0026plusmn;\u0026thinsp;4 cm/s, respectively, \u003cem\u003evs.\u003c/em\u003e 41\u0026thinsp;\u0026plusmn;\u0026thinsp;3 cm/s at baseline) and RV early GSR (2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1 and 2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1 1/s, respectively, \u003cem\u003evs.\u003c/em\u003e 1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1 1/s at baseline, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Tricuspid e\u0026rsquo; velocity also increased under dobutamine (12\u0026thinsp;\u0026plusmn;\u0026thinsp;1 cm/s \u003cem\u003evs.\u003c/em\u003e 10\u0026thinsp;\u0026plusmn;\u0026thinsp;1 cm/s at baseline, p\u0026thinsp;=\u0026thinsp;0.02). Esmolol also caused a decrease in e\u0026rsquo; wave velocity and early GSR values. Dobutamine infusion shortened the IVRT (46\u0026thinsp;\u0026plusmn;\u0026thinsp;5 \u003cem\u003evs.\u003c/em\u003e 58\u0026thinsp;\u0026plusmn;\u0026thinsp;4 ms at baseline, p\u0026thinsp;=\u0026thinsp;0.007). Early doses of endotoxin infusion prolonged the IVRT (66\u0026thinsp;\u0026plusmn;\u0026thinsp;6 ms, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 \u003cem\u003evs.\u003c/em\u003e baseline), and significant increases in E/e\u0026rsquo; and E/early GSR ratios were observed at late endotoxemia. Echocardiographic indices of RV diastolic function in patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\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\u003eEchocardiographic data obtained under hemodynamic interventions in pigs.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEsmolol\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDobutamine\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVolume\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEndotoxin early\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEndotoxin late\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of animals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart rate (bpm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84\u0026thinsp;\u0026plusmn;\u0026thinsp;3*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e118\u0026thinsp;\u0026plusmn;\u0026thinsp;4*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e99\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e89\u0026thinsp;\u0026plusmn;\u0026thinsp;4*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e114\u0026thinsp;\u0026plusmn;\u0026thinsp;4*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRV Echocardiographic volumes and indices of systolic function\u003c/b\u003e\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3D RV End-diastolic volume (ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54\u0026thinsp;\u0026plusmn;\u0026thinsp;3*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e57\u0026thinsp;\u0026plusmn;\u0026thinsp;3*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e61\u0026thinsp;\u0026plusmn;\u0026thinsp;4*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3D RV End-systolic volume (ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u0026thinsp;\u0026plusmn;\u0026thinsp;2*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u0026thinsp;\u0026plusmn;\u0026thinsp;2*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25\u0026thinsp;\u0026plusmn;\u0026thinsp;2*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29\u0026thinsp;\u0026plusmn;\u0026thinsp;2*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e38\u0026thinsp;\u0026plusmn;\u0026thinsp;2*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3D RV ejection fraction (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52\u0026thinsp;\u0026plusmn;\u0026thinsp;2*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62\u0026thinsp;\u0026plusmn;\u0026thinsp;2*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e49\u0026thinsp;\u0026plusmn;\u0026thinsp;2*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e40\u0026thinsp;\u0026plusmn;\u0026thinsp;2*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac output (L/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid DTI S' wave velocity (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u0026thinsp;\u0026plusmn;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u0026thinsp;\u0026plusmn;\u0026thinsp;0*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u0026thinsp;\u0026plusmn;\u0026thinsp;0*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7\u0026thinsp;\u0026plusmn;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6\u0026thinsp;\u0026plusmn;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u0026thinsp;\u0026plusmn;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRV Peak Global Strain (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-25\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-21\u0026thinsp;\u0026plusmn;\u0026thinsp;1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-27\u0026thinsp;\u0026plusmn;\u0026thinsp;1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-24\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-23\u0026thinsp;\u0026plusmn;\u0026thinsp;1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-16\u0026thinsp;\u0026plusmn;\u0026thinsp;1*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRV Peak Systolic GSR (1/sec)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRV Echocardiographic indices of diastolic function\u003c/b\u003e\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid E wave velocity (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49\u0026thinsp;\u0026plusmn;\u0026thinsp;4*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53\u0026thinsp;\u0026plusmn;\u0026thinsp;4*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e65\u0026thinsp;\u0026plusmn;\u0026thinsp;4*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid A wave velocity (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29\u0026thinsp;\u0026plusmn;\u0026thinsp;3*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47\u0026thinsp;\u0026plusmn;\u0026thinsp;3*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51\u0026thinsp;\u0026plusmn;\u0026thinsp;3*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e37\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e48\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid E/A ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid E Deceleration Time (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e105\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e106\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e89\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e83\u0026thinsp;\u0026plusmn;\u0026thinsp;9*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e102\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e86\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid DTI e\u0026rsquo; wave velocity (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u0026thinsp;\u0026plusmn;\u0026thinsp;1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u0026thinsp;\u0026plusmn;\u0026thinsp;1*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid DTI a\u0026rsquo; wave velocity (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u0026thinsp;\u0026plusmn;\u0026thinsp;1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11\u0026thinsp;\u0026plusmn;\u0026thinsp;1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE/e\u0026rsquo; ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u0026thinsp;\u0026plusmn;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u0026thinsp;\u0026plusmn;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17\u0026thinsp;\u0026plusmn;\u0026thinsp;1*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid DTI IVRT (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39\u0026thinsp;\u0026plusmn;\u0026thinsp;6*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e47\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e66\u0026thinsp;\u0026plusmn;\u0026thinsp;6*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e45\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRV Early Diastolic GSR (1/sec)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRV Late Diastolic GSR (1/sec)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE/RV Early Diastolic GSR ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e49\u0026thinsp;\u0026plusmn;\u0026thinsp;2*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eLeast square means and standard errors. *p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs. baseline (Dunnett\u0026rsquo;s contrasts). DTI, Doppler Tissue Imaging; SR: strain rate; GSR: global strain rate; IVRT, isovolumic relaxation time; *p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs. Baseline.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \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\u003eImaging characterization of the patient group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFallot\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePulmonary Hypertension\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRV Echocardiographic indices of diastolic function\u003c/b\u003e\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid E wave velocity (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (24\u0026ndash;53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (41\u0026ndash;57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (22\u0026ndash;29)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid A wave velocity (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (19\u0026ndash;38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (38\u0026ndash;39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (15\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid E/A ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.4 (1.1\u0026ndash;1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.4 (1.1\u0026ndash;1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.4 (1.1\u0026ndash;1.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid E Deceleration Time (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e215 (201\u0026ndash;279)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e253 (201\u0026ndash;279)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e209 (205\u0026ndash;212)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid DTI e\u0026rsquo; wave velocity (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.1 (7.6\u0026ndash;10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.6 (7.6\u0026ndash;10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.9 (7.8\u0026ndash;11.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid DTI a\u0026rsquo; wave velocity (cm/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.9 (4.6\u0026ndash;10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.9 (2.2\u0026ndash;5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.3 (9.2\u0026ndash;14.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE/e\u0026rsquo; ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5 (2.7\u0026ndash;6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.0 (3.9\u0026ndash;7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.5 (2.3\u0026ndash;4.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid DTI IVRT (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78 (47\u0026ndash;97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47 (46\u0026ndash;60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e113 (92\u0026ndash;133)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRV Early Diastolic GSR (1/sec)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9 ( 0.6. \u0026minus;\u0026thinsp;1,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.6 (1.5\u0026ndash;1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.3 (1.0\u0026ndash;1.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRV Late Diastolic GSR (1/sec)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6 (0.4\u0026ndash;0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5 (0.3\u0026ndash;0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.2 (1.1\u0026ndash;1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE/RV Early Diastolic GSR ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (32\u0026ndash;75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (20\u0026ndash;45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (17\u0026ndash;50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVC dimension (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (16\u0026ndash;20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (15\u0026ndash;20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (17\u0026ndash;19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVC collapsibility (\u0026lt;/\u0026ge; 50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2/2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCMR RV volumes\u003c/b\u003e\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCMR RV End-diastolic volume (mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e290 (148\u0026ndash;339)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e323 (297\u0026ndash;355)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e139 (118\u0026ndash;202)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCMR RV End-systolic volume (mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e169 (76\u0026ndash;198)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e175 (170\u0026ndash;198)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72 (61\u0026ndash;133)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCMR RV ejection fraction (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (36\u0026ndash;48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (37\u0026ndash;46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 (35\u0026ndash;50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eMedian (interquartile range); DTI, Doppler Tissue Imaging; SR: strain rate; GSR: global strain rate; IVRT, isovolumic relaxation time; IVC, inferior vena cava; CMR, cardiac magnetic resonance.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eRV echocardiography diastolic indices versus RV intrinsic diastolic properties and filling pressures\u003c/h2\u003e \u003cp\u003eCorrelations between echocardiographic RV diastolic indices and intrinsic RV diastolic properties and filling pressures in the animal model and clinical cohort are shown in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, \u003cb\u003eand\u003c/b\u003e Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u0026amp; \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. In animals, we only found mild positive correlations of \u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sub\u003e with the tricuspid E/A ratio (R\u003csub\u003erm\u003c/sub\u003e 0.36, p\u0026thinsp;=\u0026thinsp;0.007) and the e\u0026rsquo; velocity (R\u003csub\u003erm\u003c/sub\u003e 0.28, p\u0026thinsp;=\u0026thinsp;0.005; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In patients, IVRT showed a strong inverse relationship with mean RAP (r= -0.73, p\u0026thinsp;=\u0026thinsp;0.025) whereas RV early GSR positively correlated with RAP (r\u0026thinsp;=\u0026thinsp;0.85, p\u0026thinsp;=\u0026thinsp;0.004; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Neither tricuspid E/e\u0026rsquo; nor E/RV early diastolic GSR ratio were related with mean RAP or RVEDP in the experimental or in the clinical datasets.\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\u003eRelationship between diastolic echocardiographic indices with diastolic properties and filling pressures in the experimental and clinical studies.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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=\"char\" char=\".\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003et\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e\u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e\u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e\u0026minus;\u003c/em\u003e\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003emean RAP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003eRVEDP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnimals\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePts.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnimals\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePts.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAnimals\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePts.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAnimals\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePts.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eAnimals\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003ePts.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTricuspid E wave velocity (cm/s)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTricuspid E/A ratio\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.36*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e-0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTricuspid E Deceleration Time (ms)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e-0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e-0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e-0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTricuspid DTI e\u0026rsquo; wave velocity (cm/s)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.28*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-0.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTricuspid E/e\u0026rsquo; ratio\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e-0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTricuspid DTI IVRT (ms)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e-0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e-0.73*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-0.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRV Global Early Diastolic SR (1/sec)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.85*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eE/RV Early Diastolic GSR ratio\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e-0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e-0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e-0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e-0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003eCorrelation coefficients for repeated measures (left) and Rho Spearman values (right) for experimental and clinical cohort (Pts). *p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. t, relaxation constant; \u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sub\u003e, stiffness constant, \u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e\u0026minus;\u003c/em\u003e\u003c/sub\u003e, elastic recoil constant; RAP, right atrial pressure; RVEDP, RV end-diastolic pressure; Pts., patients; DTI, Doppler Tissue Imaging; IVRT, isovolumic relaxation time; GSR: Global Strain Rate.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePp at TVO (RV suction) positively correlated with tricuspid flow DT (R\u003csub\u003erm\u003c/sub\u003e 0.34, p\u0026thinsp;=\u0026thinsp;0.009) and was negatively related with e\u0026rsquo; and early GSR (R\u003csub\u003erm\u003c/sub\u003e -0.27 and \u0026minus;\u0026thinsp;0.33, respectively, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 for both; Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e \u003cb\u003eand\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation between RV diastolic echocardiographic indices with passive RV pressure at early filling (suction).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003ePassive pressure at TVO\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnimals\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTricuspid E wave velocity (cm/s)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTricuspid E/A ratio\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTricuspid E Deceleration Time (ms)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.34*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTricuspid DTI e\u0026rsquo; wave velocity (cm/s)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.27*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTricuspid E/e\u0026rsquo; ratio\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.29*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTricuspid DTI IVRT (ms)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRV Global Early Diastolic SR (1/sec)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.33*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eE/RV Early Diastolic GSR ratio\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.30*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eCorrelation coefficients for repeated measured/Rho Spearman for clinical/experimental datasets. *p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Exp: experimental cohort; Clin: clinical cohort; RAP, right atrial pressure; TVO: tricuspid valve opening; ED: end-diastole; DTI, Doppler Tissue Imaging; IVRT, isovolumic relaxation time; GSR: Global Strain Rate\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo our knowledge, this is the first study aimed to validate RV echocardiographic diastolic indices, addressing within- and between- subject measurements, against ventricular relaxation and passive mechanical properties \u0026ndash;elastic recoil and stiffness- obtained from PV loops data. By analyzing the full diastolic PV-time signals, from animal and clinical experiments, we demonstrate that neither the conventional pulsed-wave Doppler tricuspid inflow pattern, nor the tricuspid annulus DTI diastolic velocities or strain-derived measurements, properly account for the diastolic properties of the right ventricle. Our results highlight the limitations of Doppler echocardiography for inferring RV diastolic properties, and filling pressures.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eDeterminants of echocardiographic RV diastolic indices\u003c/h2\u003e \u003cp\u003ePV loop analyses during preload modification are the gold standard to determine intrinsic ventricular diastolic chamber properties. Conventional PV data analyses have shown the limitations of Doppler echocardiography and tissue Doppler imaging to reflect intrinsic LV diastolic properties and function [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Similarly, the current echocardiographic recommendations for assessing RV diastolic function have been recently questioned [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRV filling is governed by the right atrioventricular pressure gradient, which is driven by distinct sources of forces interacting simultaneously. It is commonly accepted that, at early diastole, relaxation and elastic recoil are responsible for RV depressurization, whereas stiffness and delayed relaxation determine the end-diastolic pressure.\u003c/p\u003e \u003cp\u003eContrary to what happens in the LV, the isovolumic relaxation phase is often absent in the normal RV [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This implies volume-dependent RV passive properties may also play a major role in early RV filling. Classically, the exponential fitting of the pressure decay at early diastole (Weiss method) has been assessed RV relaxation constant (t). However, this methodology fails to discriminate the relative contribution of restoring forces to early RV depressurization [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eClassical methods for measuring RV stiffness rely on the assumption that relaxation is completed at end-diastole [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, it is known that in chronic overloaded RVs, chamber filling is often impaired by shorter diastolic times [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Thus, prolonged τ leads to incomplete relaxation, and larger end-diastolic pressures [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This emphasizes the need for an intrinsic stiffness parameter, independent of residual relaxation. In this work, we overcome these limitations by using a method capable of decoupling ventricular relaxation and passive mechanical properties [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrevious studies using conventional relaxation analyses have shown a direct relationship between τ and E wave DT [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, as mentioned above, prolonged t obtained using the Weiss method may induce to misinterpretation. In fact, when we calculated the RV pressure diastolic components separately, we observed a negative moderate correlation between passive RV suction and E wave DT (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMitral e\u0026rsquo; has shown to be dependent on relaxation rate and restoring forces, and it is inversely related to passive stiffness [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In our experimental study, we observed a mild positive correlation between stiffness (\u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e)\u003c/em\u003e and RV passive suction (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e \u003cb\u003eand\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). This suggests stiffer RVs present higher tricuspid velocities, highlighting the stiffness contribution to early RV filling.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLimitations of echocardiography to assess right filling pressures\u003c/h2\u003e \u003cp\u003eNoninvasive estimation of filling pressures is one of the main objectives of the echocardiographic assessment of diastolic function. In the right heart, an elevated RAP is the earliest sign of a failing ventricle and determines symptoms and prognosis of many cardiovascular diseases [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Besides the diameter of the inferior vena cava and the right atrium size, tricuspid E/A and E/e\u0026rsquo; ratios are recommended indices to infer RV filling pressures [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Those recommendations are based on the hypotheses that early filling depends only on the effects of atrial pressure and the degree of the chamber depressurization, assuming a reduced early diastolic annular velocity when relaxation is impaired. Hence, eGSR has been proposed to account for right ventricular relaxation, and the E/eGSR ratio suggested to reflect RV filling pressures [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, we did not find Doppler, DTI or myocardial deformation indices to be related with elevated mean RAP in a controlled experimental setting. Specifically, in the group of patients, IVRT negatively correlated with mean RAP, whereas it positively correlated with RV eGSR. These observations deserve further exploration in larger sets of patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eClinical implications\u003c/h2\u003e \u003cp\u003eAlthough, the tricuspid inflow pattern and the E/e\u0026rsquo; ratio are included in the current echocardiographic recommendations for assessing RV diastolic function [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], there is increasing evidence that calls it into question [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Tricuspid filling and DTI parameters may be useful in some scenarios, as in the overloaded RV, to approximate filling pressures, and may provide prognosis information in the overloaded RV [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. However, our results highlight their limitations.\u003c/p\u003e \u003cp\u003eIn this work, we demonstrate that some of the conventional and myocardial deformation indices are unable to reflect the impact of different hemodynamic conditions on the intrinsic diastolic properties and filling pressures of the RV. Moreover, our work shows traditional noninvasive indices do not reflect therapeutic changes in RV pathologies. Multi-parametrical algorithms, combining several Doppler and morphological parameters \u0026mdash;as currently recommended to evaluate LV diastolic function and filling pressures- [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] should be specifically validated for the RV.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eWe acknowledge the number of studied patients is small. However, we believe our results, combining clinical and experimental models, provide sufficient evidence to serve as a proof of concept for future studies.\u003c/p\u003e \u003cp\u003eAnimal studies of acute RV modulation may not be extensible to chronic scenarios of RV overload and were performed under general anesthesia, which may explain the differences between the clinical and animal datasets. Late phase of endotoxemia is characterized by a systemic inflammatory syndrome, similar to sepsis. This may explain the low mean RAP observed during those phases, despite the presence of RV dysfunction.\u003c/p\u003e \u003cp\u003eSome echocardiographic parameters related to RV diastolic function and mean RAP, such as right atrial size and deformation, suprahepatic flow pattern, or combined parameters of the above [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], were not analyzed.\u003c/p\u003e \u003cp\u003eOf note, intraventricular fluid dynamics play an important role in the filling of normal and remodeled LVs [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, its impact on the RV filling has not been addressed.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eCurrently recommended Doppler, DTI and strain-based ultrasound indices of RV diastolic function weakly account for the intrinsic RV chamber diastolic properties. These findings suggest that current recommendations for the assessment of RV diastolic function and filling pressures in the clinical setting should be revisited.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eDTI\u003c/strong\u003e Doppler tissue imaging\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGSR\u003c/strong\u003e\u0026nbsp; \u0026nbsp; Early global longitudinal diastolic strain-rate\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIVC\u003c/strong\u003e Inferior vena cava\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIVRT\u003c/strong\u003e Isovolumetric relaxation time\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePV\u003c/strong\u003e Pressure-volume\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRAP\u003c/strong\u003e Right atrial pressure\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eThe clinical study protocol complied with the Declaration of Helsinki and was approved by the Committee on Ethics in Drug Research of the Gregorio Mara\u0026ntilde;\u0026oacute;n Health Research Institute (282/12 and 335/16). All patients provided written informed consent to participate in the study.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eThe data underlying this article will be shared on request to the corresponding author.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003e\u0026nbsp; The authors declare no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding Sources\u003c/h2\u003e\n\u003cp\u003eThis work was supported by grants PI12/02885 (to JB); CM12/00273 and JR15/00039 (to CPV); and PI16/01237 (to CPV and RP-A) from the Instituto de Salud Carlos III and by the EU \u0026ndash; European Regional Development Fund. CPV was also funded by Gerencia Regional de Salud de Castilla y Le\u0026oacute;n (INT/M/10/23).\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eAuthors\u0026apos; contributions\u003c/h2\u003e\n\u003cp\u003eC.P.d.V., R.P.A. and J.B. conception and design of research; C.P.d.V., R.P.A., D.R.-P., P.M.-L., Y.B., M.M.D., A.D.M., R.C.B. and J.C.A. performed experiments; C.P.d.V., R.P.A., P.M.-L., Y.B., A.D.M., C.H.F. and R.C.B. analyzed data; C.P.d.V., R.P.A., P.M.-L and J.B. interpreted results of experiments; C.P.d.V. and P.M.-L. prepared figures; C.P.d.V., R.P.A. and P.M-L drafted manuscript; J.B., C.P.d.V., R.P.A., P.M.-L., D.R.-P, Y.B., A.D.M., C.H.F., R.C.B., J.B. and F.F.A edited and revised manuscript; all authors approved final version of manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003cbr\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHaddad F, Doyle R, Murphy DJ, Hunt SA. 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J Appl Physiol. 2014;116(4):355\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRain S, Handoko ML, Trip P, Gan CT, Westerhof N, Stienen GJ, et al. Right ventricular diastolic impairment in patients with pulmonary arterial hypertension. Circulation. 2013;128(18):2016.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685\u0026ndash;713. quiz 86\u0026thinsp;\u0026ndash;\u0026thinsp;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkumura K, Slorach C, Mroczek D, Dragulescu A, Mertens L, Redington AN, et al. Right ventricular diastolic performance in children with pulmonary arterial hypertension associated with congenital heart disease: correlation of echocardiographic parameters with invasive reference standards by high-fidelity micromanometer catheter. Circ Cardiovasc Imaging. 2014;7(3):491\u0026ndash;501.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoriyama H, Murata M, Tsugu T, Kawakami T, Kataoka M, Hiraide T, et al. The clinical value of assessing right ventricular diastolic function after balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension. Int J Cardiovasc Imaging. 2018;34(6):875\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiLorenzo M, Hwang WT, Goldmuntz E, Ky B, Mercer-Rosa L. Diastolic dysfunction in tetralogy of Fallot: Comparison of echocardiography with catheterization. Echocardiography. 2018;35(10):1641\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShima H, Tsujino I, Nakamura J, Nakaya T, Sugimoto A, Sato T, et al. Exploratory analysis of the accuracy of echocardiographic parameters for the assessment of right ventricular function and right ventricular-pulmonary artery coupling. Pulm Circ. 2024;14(2):e12368.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBermejo J, Yotti R, del Perez C, del Alamo JC, Rodriguez-Perez D, Martinez-Legazpi P, et al. Diastolic chamber properties of the left ventricle assessed by global fitting of pressure-volume data: improving the gold standard of diastolic function. J Appl Physiol (1985). 2013;115(4):556\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCortina C, Bermejo J, Yotti R, Desco MM, Rodriguez-Perez D, Antoranz JC, et al. Noninvasive assessment of the right ventricular filling pressure gradient. Circulation. 2007;116(9):1015\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYotti R, Bermejo J, Benito Y, Antoranz JC, Desco MM, Rodriguez-Perez D, et al. Noninvasive estimation of the rate of relaxation by the analysis of intraventricular pressure gradients. Circ Cardiovasc Imaging. 2011;4(2):94\u0026ndash;104.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlkon J, Humpl T, Manlhiot C, McCrindle BW, Reyes JT, Friedberg MK. Usefulness of the right ventricular systolic to diastolic duration ratio to predict functional capacity and survival in children with pulmonary arterial hypertension. Am J Cardiol. 2010;106(3):430\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChowdhury SM, Goudar SP, Baker GH, Taylor CL, Shirali GS, Friedberg MK, et al. Speckle-Tracking Echocardiographic Measures of Right Ventricular Diastolic Function Correlate with Reference Standard Measures Before and After Preload Alteration in Children. Pediatr Cardiol. 2017;38(1):27\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKasner M, Westermann D, Steendijk P, Gaub R, Wilkenshoff U, Weitmann K, et al. Utility of Doppler echocardiography and tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction: a comparative Doppler-conductance catheterization study. Circulation. 2007;116(6):637\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePagourelias ED, Efthimiadis GK, Parcharidou DG, Gossios TD, Kamperidis V, Karoulas T, et al. Prognostic value of right ventricular diastolic function indices in hypertrophic cardiomyopathy. Eur J Echocardiogr. 2011;12(11):809\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, et al. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016;29(4):277\u0026ndash;314.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartinez-Legazpi P, Bermejo J, Benito Y, Yotti R, Del Perez C, Gonzalez-Mansilla A, et al. Contribution of the diastolic vortex ring to left ventricular filling. J Am Coll Cardiol. 2014;64(16):1711\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"cardiovascular-ultrasound","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"caru","sideBox":"Learn more about [Cardiovascular Ultrasound](http://cardiovascularultrasound.biomedcentral.com/)","snPcode":"12947","submissionUrl":"https://submission.nature.com/new-submission/12947/3","title":"Cardiovascular Ultrasound","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"diastolic function, right ventricle, elastic recoil, relaxation, stiffness, echocardiography","lastPublishedDoi":"10.21203/rs.3.rs-6339436/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6339436/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe reliability of the recommended echocardiographic methods for assessing RV diastolic function has been questioned. We aimed to validate noninvasive indices of RV diastolic function, derived from tricuspid Doppler and myocardial deformation metrics, against intrinsic diastolic chamber properties and filling pressures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe obtained simultaneous high-fidelity pressure-volume loops and echocardiographic data in separate animal and clinical settings: 1) a porcine model of acute hemodynamic interventions (n = 13), and 2) patients with Fallot tetralogy and pulmonary hypertension (n = 9). These designs allow for within- and between-subject validation. From the PV loops data, we obtained the reference values of RV stiffness (\u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sub\u003e), elastic recoil (\u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e−\u003c/em\u003e\u003c/sub\u003e) and relaxation (τ) constants, as well as the contribution of passive properties to instantaneous diastolic pressures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the animal setting, only the tricuspid E/A ratio and e’ velocity weakly correlated with \u003cem\u003eS\u003c/em\u003e\u003csub\u003e\u003cem\u003e+\u003c/em\u003e\u003c/sub\u003e (R\u003csub\u003erm\u003c/sub\u003e:0.36 and 0.28 respectively, p \u0026lt; 0.01 for both). In the clinical group, no correlation was found between the echocardiographic indices and the intrinsic diastolic properties. Isovolumic relaxation time and early diastolic global strain-rate (GSR) correlated with mean right atrial pressure (RAP) (Spearman r: -0.73 and 0.85, respectively, p \u0026lt; 0.05 for both). E/e’ and E/GSR ratio were not associated with RAP. Tricuspid e’ and GSR negatively correlated with passive pressure component (only due to) at valve opening (R\u003csub\u003erm\u003c/sub\u003e -0.27 and − 0.33, respectively, p \u0026lt; 0.01 for both).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRecommended echocardiographic indices of RV diastolic function do not reflect intrinsic RV diastolic properties. Therefore, the application of these indices for inferring RV diastolic function and filling pressures is limited.\u003c/p\u003e","manuscriptTitle":"Validation of Noninvasive Indices of Right Ventricular Diastolic Function. Simultaneous Echocardiography and Pressure-volume Catheterization Studies","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-10 08:07:58","doi":"10.21203/rs.3.rs-6339436/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-29T12:20:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-24T12:38:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-24T12:04:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"313797599136103187428900906645524707903","date":"2025-04-20T07:41:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"281880887965272918276403628332239619337","date":"2025-04-15T02:08:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"24043458131847766792383569085930170651","date":"2025-04-07T13:55:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-07T09:20:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-02T05:57:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-02T05:54:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"Cardiovascular Ultrasound","date":"2025-03-30T15:55:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cardiovascular-ultrasound","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"caru","sideBox":"Learn more about [Cardiovascular Ultrasound](http://cardiovascularultrasound.biomedcentral.com/)","snPcode":"12947","submissionUrl":"https://submission.nature.com/new-submission/12947/3","title":"Cardiovascular Ultrasound","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fe57b998-278c-48bb-b109-473e72e7f44c","owner":[],"postedDate":"April 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-14T16:00:44+00:00","versionOfRecord":{"articleIdentity":"rs-6339436","link":"https://doi.org/10.1186/s12947-025-00351-5","journal":{"identity":"cardiovascular-ultrasound","isVorOnly":false,"title":"Cardiovascular Ultrasound"},"publishedOn":"2025-07-09 15:57:15","publishedOnDateReadable":"July 9th, 2025"},"versionCreatedAt":"2025-04-10 08:07:58","video":"","vorDoi":"10.1186/s12947-025-00351-5","vorDoiUrl":"https://doi.org/10.1186/s12947-025-00351-5","workflowStages":[]},"version":"v1","identity":"rs-6339436","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6339436","identity":"rs-6339436","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}