Echocardiographic Determinants of Oxygen Uptake During Exercise in Patients with repaired Tetralogy of Fallot and Severe Pulmonary Regurgitation

Echocardiographic Determinants of Oxygen Uptake During Exercise in Patients with repaired Tetralogy of Fallot and Severe Pulmonary Regurgitation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Echocardiographic Determinants of Oxygen Uptake During Exercise in Patients with repaired Tetralogy of Fallot and Severe Pulmonary Regurgitation Sahar Alborikan, aeshah Althunayyan, Bejal Pandya, katherine Vonklemperer, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5342548/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Reduced exercise capacity in patients with repaired Tetralogy of Fallot cannot be explained wholly by severe pulmonary regurgitation alone. We investigated the effect of pulmonary regurgitation and other measures of left and right ventricular function to identify the principal determinants of exercise performance. Methods: 100 patients with TOF were evaluated, 60 with severe PR and 40 with no or minimal PR. Patients underwent cardiopulmonary exercise testing with concurrent echocardiography. Echocardiography was performed at rest and during exercise (both at low and high intensity for the appropriate parameters). Contractile reserve was expressed as the percentage increase at the relevant time point. Univariate and multivariate linear regression was used to generate a predictive model for exercise function. Results: There was no difference in exercise performance between those with and without pulmonary regurgitation when judged by peak absolute oxygen consumption VO 2 (1695±627vs1744±521, ml/min, p>0.05), or a range of other submaximal cardiopulmonary parameters. Right ventricular volumes were higher in those with pulmonary regurgitation while left ventricular long axis function was reduced. There were no associations between exercise measures with the degree of pulmonary regurgitation and right ventricular volume at rest or during exercise. There was lower contractile reserve of the right ventricle in those with pulmonary regurgitation (fractional area change 20±15 % vs 23±16 %, p<0.05) balanced by improved reserve of the left ventricle. Augmentation of the left ventricular global longitudinal strain and right ventricular fractional area curve together showed the strongest association with peak VO 2 . Conclusions: There was an overall marked reduction in exercise capacity in patients with repaired tetralogy of Fallot, but no difference between those with and without PR. The degree of exercise limitation is more dependent upon the ability of right and left ventricles. peak oxygen consumption cardiopulmonary exercise testing echocardiography pulmonary regurgitation. Figures Figure 1 Figure 2 Introduction Chronic pulmonary regurgitation (PR) remains the most common hemodynamic complication in adult patients with repaired Tetralogy of Fallot (rTOF) ( 1 , 2 ). Current guidance supports intervention on the pulmonary valve where regurgitation is severe and the patient experiences symptoms (Class I), and progressive right ventricular (RV) dilatation (Class IIa) ( 3 ). Despite this, the precise source of progressive functional limitation in TOF is not fully established ( 4 , 5 ). Left and right ventricular performance ( 6 , 7 ) as well as physical deconditioning may also be important ( 2 ). This matters in predicting the likely symptomatic benefit from intervention. Previous reports have demonstrated only a limited objective symptomatic benefit for reintervention on the pulmonary valve in this circumstance ( 8 ). In this prospective cohort study, we hypothesised that more complex mechanisms than the presence of severe PR would be responsible for exercise limitation. To test this, we evaluated patients with rTOF and severe PR, comparing them to a group of patients with no, or negligible PR to establish which echocardiographic parameters were most strongly associated with oxygen uptake (VO 2 peak) and other objective markers of exercise performance. Methods Study design and population We prospectively recruited adult patients with severe PR after previous TOF repair and a control group with previous TOF repair and negligible or absent PR. Inclusion criteria were 1) diagnosis of repaired TOF; 2) NYHA status less than III; The presence of severe PR was determined by integrated echocardiographic criteria. All patients also underwent clinical cardiac MRI to confirm the diagnosis and the absence of ancillary lesions. Exclusion criteria included significant pulmonary stenosis, right ventricular outflow tract (RVOT) obstruction, severe left ventricular outflow obstruction, RV-Pulmonary artery conduit, ventricular arrhythmias, pacemaker, significant pulmonary hypertension, inability to exercise on the exercise bicycle and poor acoustic windows. Echocardiography Echocardiography was performed using a VIVID E95 (Vingmed-General Electric, Horten, Norway) ultrasound platform. Standard 2D, M-mode, colour Doppler, pulsed, continuous wave and colour tissue Doppler were performed according to British Society of Echocardiography guidelines ( 9 ). In order to facilitate strain analyses, a frame rate was selected between 35 and 70 frames per second. For 3 dimensional LV and RV analyses, a full volume chamber focused single beat acquisitions were stored with a frame rate not less than 30 (Hz) during end-expiratory breath-hold (utilizing multibeat acquisition when required). Normal reference ranges were taken from a range of contemporary sources ( 9 ). Strain analysis was performed offline on the GE Echopac workstation. For the LV, a region of interest was defined in three apical views creating 17 individual regions of interest for regional strain analysis. Individual strain curves were generated for each individual segment, and end systole was defined by aortic valve closure in the 3-chamber view. The GLS was defined as the average of all 17 segments at end systole. For the RV, a similar region of interest was established from the basal septum to the RV apex and then to the tricuspid annulus. The RV was segmented into 3 septal segments and 3 free wall segments. The global RV global longitudinal strain (RV GLS) was the average of all segments while the free wall strain was measured in 3 segments only. All tracking was confirmed manually and in this study we only used the longitudinal component of cardiac function ( 10 , 11 ). Exercise echocardiographic tests were undertaken following a specific image acquisition protocol (Appendix A, Fig. 1 ). Imaging was undertaken at baseline and at low intensity exercise (defined as 65–75% peak age predicted heart rate). Peak exercise acquisitions were taken after the respiratory exchange ratio (RER) was > 1.0. This provided a standardised heart rate independent point beyond ventilatory threshold but with sufficient remaining exercise time to allow measurements to be made during high intensity exercise. The following measures were made at baseline and peak stages including RV and LV size function, pulmonary regurgitation and 3D volume. Strain imaging was not undertaken at high intensity exercise because of the effect of heart rate on analysis algorithms ( 12 ). Contractile reserve (CR) was the percentage increase in each parameter during exercise at either peak or low intensity exercise depending on the known behavior of the parameter (e.g parameters which plateau or where there are specific software limitations such as GLS). Cardiopulmonary exercise testing (CPET) Cardio pulmonary exercise testing was performed according to exercise testing protocol ( 13 ) on a semi-recumbent tilting cycle ergometer (ERG 911 S/L, Schiller, Switzerland). Maximum oxygen uptake (V̇O 2 peak) was continuously measured using a calibrated breath-by-breath analyzer (Cosmed Quark CPET, Rome, Italy). Peak oxygen consumption (V̇O 2 ), carbon dioxide production (VCO 2 ), and minute ventilation (VE) were acquired breath-by‐breath and averaged over a 10‐second interval. Exercise protocols were individually determined based on the patient functional status with work rate (5-20W) increased every minute until voluntary exhaustion. Heart rate (HR), blood pressure, and oxygen saturation were monitored throughout. A RER > 1 was used to indicate adequate effort. peak V̇O 2 was the highest value from an average of 30 seconds during the final stage of the exercise test. Oxygen Uptake Efficiency Slope (OUES) defined as the regression slope between V̇O 2 and Log minute ventilation (Ve), and ventilatory efficiency defined as the ratio of VE/VCO 2 expressed as the slope function between VT and before respiratory compensation point. Peak V̇O 2 values less than 84%, VE/VCO2 > 34, and an OUES < 80%, were considered abnormal (14, 15). Statistical analyses VO 2 peak was the primary end point for the study. We estimated a sample size of 25 in the cases and controls and this would permit the detection of a 30% (clinically meaningful difference between the groups). We recruited 2:1 in favor of severe PR to permit the assessment of clinical and echocardiographic predictors of exercise performance in this group. Continuous variables were presented as mean and standard deviations (SD). Student’s t tests were performed for all parameters. Univariate correlation analyses were constructed to determine relationships between hemodynamic echocardiographic and exercise parameters. Multivariate regression analysis model was constructed for absolute VO 2 (ml/min) for this regression PR was treated as a categorical variable. All statistical analyses were performed using IBM SPSS statistics version 27 (IBMCorp, London, United Kingdom). The study was approved by the Health Research Authority-Queen Square Research Ethics Committee (18/LO/0092). Results 120 patients were recruited, of whom 20 patients were excluded due to severity of pulmonary stenosis, inability to exercise or right ventricular arrythmia, leaving 100 patients, 60 with severe PR and 40 controls. Baseline characteristics are presented in table 1. The PR group was older (35±13 vs 33±11, years, p<0.05) and were marginally more frequently male. PR group also had higher frequency of transannular patch (TAP) (85 vs 68, %, p<0.05) as the primary operation. 9 patients with PR (15%) had previous reintervention with surgical pulmonary valve replacement, compared to 21 patients (53%) in the no PR subjects. The average of individualised exercise protocols was 15w (range 5-20W). A RER of >1.01 was achieved in 97 patients, with a mean value of 1.2±.1 in both groups. The termination of exercise was either due to leg fatigue, shortness of breath or general fatigue. Table 1. Baseline charactristics. Baseline characteristics Severe PR group Mean± SD No PR group Mean± SD P value Age (yrs) Sex 35 ±13 33±11 <0.05 Male Female 31 (52%) 29 (48%) 19 (48%) 21(52%) <0.05 Height (cm) 166±11 169±8 <0.05 Weight (kg) 71±16 73±14 <0.05 BMI (Kg/m 2 ) 25±5 26±5 NS ORS duration (ms) 153±20 150±22 NS Type of surgery TAP Other RVOT intervention 51 (85%) 9 (15%) 27 (68%) 13 (32%) <0.05 <0.05 BMI=body mass index; TAP= transannular patch. * Bold values indicate significant level (p<.05); NS=non-significant. There was no difference in objective exercise performance between patients with and without severe PR. The average exercise time was 10±2 minutes in the PR group and 9±1 minutes in the no PR group (P>0.05) with similar maximal workload achieved (150±55 vs 151±49 W, p>0.05) (Table2). These results were mirrored in the metabolic exercise testing where VO 2 (1695±627, ml/min vs 1744±521, ml/min, p>0.05) was similar between the two groups (Figure 1a). 48 patients (80%) fell below the normal range for predicted VO 2 in the PR group, compared to 28 patients (70%) in the control group (p>0.05, Table 2). We also demonstrated no difference across the pre-specified submaximal measure of exercise performance including OUES (1885±722 vs 1869±543, ml/min/l/min, p>0.05), and ventilatory efficiency where the VE/VCO 2 slope was not different (26±4 vs 25±5, p>0.05) (Table 2, Figure 1b and c). Table 2. Cardiopulmonary exercise performance and the difference between severe PR and no PR groups. CPET parameters Severe PR group Mean± SD No PR group Mean ± SD P value Max effort measures Exercise duration (min) Exercise protocol (w) Peak oxygen uptake VO 2 (ml/min) Peak oxygen consumption VO 2 (ml/kg/min) Peak percent of predicted VO 2 (%) Impaired peak percent of predicted VO 2 (%) Peak RER Peak HR (beat/min) Predicted HR (%) SBP at peak (mmHg) Peak workload (W) Peak workload predicted (%) O 2 saturation (%) Peak O 2 pulse (ml/beat) Predicted O 2 pulse (%) Peak VE/VCO 2 10±2 15 1695±627 24±7 75±17 67 ±14 1.2±.1 150±20 81±10 192±33 150±55 90±29 97±1 11±4 91±18 31±5 9±1 15 1744±521 25±7 76±17 68 ±11 1.2±.1 155±19 84±10 185±26 151±49 88±23 98±1 11±3 92±19 30±5 NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS Sub max effort measures VE/VCO 2 at AT VE/VCO 2 slope OUES (ml/min/l/min) Predicted OUES (%) 28 ±3 26±4 1885±722 73±20 28±5 25±5 1869±543 74±18 NS NS NS NS VO 2 =peak absolute maximum oxygen uptake in absolute (ml/min), relative (ml/kg/min), percent of predicted (%); RER=respiratory exchange ratio; HR=heart rate; SBP=systolic blood pressure; O 2 pulse=oxygen uptake divided by heart rate peak and predicted; VE/VCO 2 =the relationship between minute ventilation and carbon dioxide production at peak, at anaerobic threshold, and slope; OUES= Oxygen uptake efficiency slope peak and predicted. NS=non-significant. Full echocardiographic dataset is presented in table 3. The PR group had greater RV dimensions and volumes with 73% demonstrating RV diastolic and systolic volumes above the normal range, compared with 28% of controls (Table 3). RV fractional area change was similar in both groups (44±6 vs 42±6, %, p>0.05, Table 3), but RVGLS and RV global free wall strain (RVGFWS) were generally lower (better function) in the PR group. Right ventricular CR was however lower in the PR group, this was true for velocity augmentation; longitudinal excursion; and RV fractional area change. RVGLS in the PR group increased by 16% compared with 20% in controls (p0.05) (Table 3). LVEF and velocity augmentation (LVS) were similar in both groups. LV global longitudinal strain (LVGLS) was not different between groups with a GLS <-20% in 95% and 100% respectively (Table 3). Higher left ventricular longitudinal CR as measured by LVEF, LVS’ and longitudinal excursion, but not GLS, were observed in the PR group (Table 4). Table 3. Baseline echocardiographic difference. Baseline RV parameters Severe PR group Mean ± SD No PR group Mean ± SD P value Baseline LV parameters Severe PR group Mean ± SD No PR group Mean ± SD P value 2D Structure and function RVD Mid (cm) RVD Basal (cm) RVEDA (cm 2 ) RVESA (cm 2 ) FAC (%) TAPSE (mm) RVS’ (cm/s) RA (cm 2 ) Pulmonary Regurgitation PR PG (mmHg) PR PHT (ms) PR index PACT (ms) DSTVI TR (mmHg) PASp (mmHg) 3D Volume and function RVEDV (ml) RVEDVI (ml/m 2 ) RVESV (ml) RVESVI (ml/m 2 ) RVEF (%) RVSV (ml/m 2 ) RVSVI (ml/m 2 ) TAPSI (mm) FAC (%) 4±.5 5±.3 28±6 16±4 43±6 17±3 8±2 19±5 22±8 84±22 .4±.1 147±27 1.2±.33 23±10 35±7 179±51 101±26 88±31 50±16 51±7 91±27 51±14 17±3 44±6 3.4±.5 4.1±.6 22±6 13±4 41±5 14±4 6±2 17±4 - - - - - 18±9 32±8 128±30 70±14 67±21 37±10 48±8 62±15 34±8 13±5 42±6 <0.05 <0.05 <0.05 <0.05 NS <0.05 <0.05 <0.05 - - - - - <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 NS 2D Structure and function LVEDD (mm) LVESDD (mm) LVEF (%) MAPSE (mm) LVS’ (cm/s) E/A E’ (cm/s) E/e’ 3D Volume and function LVEDV (ml) LVEDVI (ml/m 2 ) LVESV (ml) LVESVI (ml/m 2 ) LVEF (%) LV SV (ml) LVSVI (ml/m 2 ) CO (l/m) 2D Strain RVGLS (%) RVGFWS (%) LVGLS (%) 38±6 26±5 58±5 17±2 7±3 1.5±.4 8±2 10±5 110±29 67±20 46±14 29±13 59±4 64±16 39±13 5±1 -17±3 -19±3 -15±2 39±8 27±6 59±5 15±3 7±6 1.3±.3 6±2 13±4 105 ±13 58±8 44±8 24±4 58±4 55±9 33±5 4±.7 -15±3 -17±3 -15±3 NS NS NS <0.05 NS NS <0.05 <0.05 NS <0.05 NS <0.05 NS <0.05 <0.05 NS <0.05 <0.05 NS RVD mid=right ventricular mid-size; RVD base=right ventricular basal-size; RVEDA=right ventricular end diastolic area; RVESA=right ventricular end systolic area; FAC=fractional area change; TAPSE=tricuspid annular plane systolic excursion; RVS’=right ventricular systolic velocity; RA=right atrium; PR PG=pulmonary regurgitation pressure gradient; PR PHT=pulmonary regurgitation pressure half time; PR index=severe pulmonary regurgitation index; PACT=pulmonary acceleration time; DSTVI=the ratio of diastolic and systolic time-velocity integrals; TR=tricuspid regurgitation; PASp=pulmonary artery systolic pressure; RVEDV=right ventricular end diastolic volume; RVEDVI=indexed right ventricular end diastolic volume; RVESV=right ventricular end systolic volume; RVESVI=indexed right ventricular end systolic volume; RVEF=right ventricular ejection fraction; RVSV=right ventricular stroke volume; RVSVI=indexed right ventricle stroke volume. Bold values indicate significant level (p<0.05); LVEDD=left ventricular end diastolic diameter; ; LVESD=left ventricular end systolic diameter; LVEF=left ventricular ejection fraction; MAPSE=mitral annular systolic excursion; ; LVS’= Averag left ventricular systolic velocity; E/A= r atio between E-wave and A-wave; E’ average= average of septal and lateral early mitral inflow velocity; E / e’=ratio between early mitral inflow velocity and mitral annular early diastolic velocity; LVEDV=left ventricular end diastolic volume; LVEDVI= indexed left ventricular end diastolic volume; LVESV=left ventricular end systolic volume; LVESVI=indexed left ventricular end systolic volume; LVEF= left ventricular ejection fraction; LVSV=left ventricular stroke volume; LVSVI=indexed left ventricular stroke volume; CO=cardiac output. Bold values indicate significant level (p<0.05); RVGLS=right ventricular global longitudinal strain; RVGFWS=right ventricular global free wall stain; LVGLS=left ventricular global longitudinal strain. Bold values indicate significant level (p1 Functional and Volumetric CR parameters Severe PR group Mean ± SD No PR group Mean ± SD P value Right Ventricle Δ FAC (%) Δ TAPSE (%) Δ RVS’ (%) Left ventricle Δ LVEF (%) Δ MAPSE (%) Δ LVS’ average (%) Δ LVEDV (%) Δ LVEDVI (%) Δ LVESV (%) Δ LVESVI (ml/m 2 ) Δ LVSV (ml) Δ LVSVI (ml/m 2 ) Δ CO Strain parameters ΔRVGLS (%) ΔRVGFWS (%) ΔLVGLS (%) 20±15 39±28 41±28 26±9 37±17 67±34 -16±14 -19±17 -38±18 -40±22 3±11 3±14 84±44 16±13 7±6 15±14 23±16 42±28 48±20 24±6 33±21 61±28 -13±8 -13±9 -35±13 -34±13 -2±2 -4±8 62±48 20±19 13±12 16±15 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 NS ΔFAC=contractile reserve of fractional area change; ΔTAPSE=contractile reserve of tricuspid annular plane systolic excursion; ΔRVS’=contractile reserve of right ventricular systolic velocity; ΔRVEF=contractile reserve of right ventricle ejection fraction; ΔRVSV= contractile reserve of right ventricular stroke volume; ΔRVSVI= contractile reserve of indexed right ventricle stroke volume; ΔMAPSE=contractile reserve of mitral annular systolic excursion; ΔLVS’=contractile reserve of left ventricular systolic velocity; ΔLVEDV=contractile reserve of left ventricular end diastolic volume; ΔLVEDVI=contractile reserve of indexed left ventricular end diastolic volume; ΔLVESV=contractile reserve of left ventricular end systolic volume; ΔLVESVI=contractile reserve of indexed left ventricular end systolic volume; ΔLVSV=contractile reserve of left ventricular stroke volume; ΔLVSVI=contractile reserve of indexed left ventricular stroke volume; ΔCO=contractile reserve of cardiac output. Bold values indicate significant level (p<0.05); ΔRVGLS=contractile reserve of right ventricular global longitudinal strain; ΔRVGFWS=contractile reserve of right ventricular global free wall stain; ΔLVGLS=contractile reserve of left ventricular global longitudinal strain. Bold values indicate significant level (p<0.05); NS=non-significant. None of the quantification parameters of which describe pulmonary regurgitation were correlated with peak oxygen consumption (Table 5). Across both groups, resting RV parameters including FAC, RV stroke volume (RVSV) and RVGFWS were associated with peak VO 2 . Similarly, some resting parameters of LV systolic and diastolic function showed correlation with VO 2 . In multivariate modelling change in left ventricular long axis reserve (expressed as change in GLS) (r=-.55, p<0.05), and RV fractional area change (r=.45, p<0.05) were the most important associations with peak oxygen consumption (model R 2 = .48, p<0.001, Table 5, Figure 2). Table 5. Determinants of peak absolute VO 2 (ml/min). Variables N=100 VO 2 (ml/min) Contractile reserve Δ P value Multivariate (VO 2 , ml/min) PR (0/1) R 2 = .48, p<0.001 P value Left ventricle 2D analyses Baseline (R) Peak stress (R) R - R R 2 - 2DLVEF .09 .02 .49* <0.001 .45 .56 NS LVS’ average, cm/s .12 .30 .35* <0.001 .22 .31 NS MAPSE, mm .04 .10 .06 NS - E/e’ -.32* -.10 .10 NS .36 .44 NS LVGLS (%) .20 -.30* -.50** <0.001 -.55 .40 <0.05 3D Analyses LVEDV, ml .16 .15 .15 NS - NS LVEDVI, ml/m 2 .17 .11 .11 NS - NS LVESV, ml -.15 -.06 .05 NS - NS LVESVI, ml/m 2 .11 .03 .06 NS - NS LVSV, ml .12 .03 .00 NS - NS LVSVI, ml/m 2 .27* .17 .10 NS .11 .30 NS Right ventricle 2D analyses RVD mid (cm) -.36 .01 .22 NS - RVD basal (cm) .20 -.04 .01 NS - TAPSE (mm) -0.16 .27** .20 NS - FAC (%) .37* .39* .40* <0.001 .45 .35 <0.05 RVS’ (cm/s) .04 -.00 .10 NS - RVGLS (%) .24 .17 .33 NS - - RVGFWS (%) .46** .25 .11 NS .26 .37 NS 3D Analyses RVEDV (ml) .11 -.05 .18 NS - - RVEDVI (ml/m2) .11 -.00 .06 NS - - RVESV (ml) .05 -.15 .01 NS - - RVESVI (ml/m 2 ) .08 -.12 .07 NS - - RVEF (%) -55 .23 .11 NS - - RVSV (ml) .39* .05 .02 NS - - RVSVI (ml/m 2 ) .09 .09 .10 NS - - Pulmonary regurgitation PR PG (mmHg) .22 .34 .07 NS - - PR Index .03 .13 .11 NS - - PHT (ms) .33 .11 .03 NS - - DSTVI -.04 .10 -.07 NS - - LVEF=left ventricular ejection fraction; MAPSE=mitral annular systolic excursion; ; LVS’=left ventricular systolic velocity; E/e’=ratio between early mitral inflow velocity and mitral annular early diastolic velocity; LVEDV=left ventricular end diastolic volume; LVEDVI=indexed left ventricular end diastolic volume; LVESV=left ventricular end systolic volume; LVESVI=indexed left ventricular end systolic volume; LVEF=left ventricular ejection fraction; LVSV=left ventricular stroke volume; LVSVI=indexed left ventricular stroke; RV mid=right ventricular mid-size; RV base=right ventricular basal-size; TAPSE=tricuspid annular plane systolic excursion; FAC=fractional area change; RVS’=right ventricular systolic velocity; RVEDV=right ventricular end diastolic volume; RVEDVI= indexed right ventricular end diastolic volume; RVESV=right ventricular end systolic volume; RVESVI=indexed right ventricular end systolic volume; RVEF=right ventricular ejection fraction; RVSV=right ventricular stroke volume; RVSVI= indexed right ventricle stroke volume. Bold values indicate significant level (p<0.05); PG=pulmonary regurgitation pressure gradient; PR index=severe pulmonary regurgitation index; RVGLS=right ventricular global longitudinal strain; RVGFWS=right ventricular global free wall stain; LVGLS=left ventricular global longitudinal strain. ΔFAC=contractile reserve of fractional area change; ΔLVGLS=contractile reserve of left ventricular global longitudinal strain. Bold values indicate significant level (p<0.05). Discussion We have demonstrated that in patients with rTOF those with severe pulmonary regurgitation have the same objective exercise capacity as those with only mild or no valve incompetence despite evidence of RV remodeling and dilatation. Exploratory echocardiographic analyses suggest that the functional parameters of both the right and left ventricles, especially under stress conditions, rather than the presence of PR or RV remodeling, are the most important, accounting together for nearly 50% of the variability in VO 2 . The functional limitations we observed is in keeping with most previous studies ( 16 – 18 ), and with a recent systematic review that showed an overall mild exercise intolerance with a peak predicted VO 2 of 68% ​± ​2.8 ( 19 ). Many factors including the choice of surgical approach (especially transannular patch) ( 19 ), latent left ventricular dysfunction, often with a preserved EF ( 7 ), the effect of ventricular interdependency ( 21 ), and restrictive RV physiology ( 22 ) may also play an important role over and above a simple regurgitation / right ventricular volume model. Current guidelines for intervention are however based on observational data and the precise balance between volumes and function as predictors of exercise ability is less well understood ( 3 , 23 ). In this study as expected, there was a marked reduction in exercise capacity across all patients, however patients with severe PR and patients with mild or no PR had no difference in oxygen uptake (VO 2 ), Oxygen Uptake Efficiency Slope (OUES) or ventilatory efficiency (VE/VCO2 slope) despite being well balanced and without major confounders. Other than a slight difference in age and the frequency of TAP surgery, there were no substantial confounders. While there is often an observed disconnect between the perception of the symptom of breathlessness and VO 2 max ( 17 , 24 ), our data also shows the same finding for submaximal effort parameters (which allows for those subjects who were unable to reach RER > 1.1), and ventilatory efficiency which is more closely linked to the perception of breathlessness ( 25 ). As expected, the right ventricular myocardial volumes were larger in the severe PR group consistent with multiple previous investigations( 21 , 26 ). RV longitudinal functional abnormalities were observed in both groups and, interestingly the measures of RV function were slightly worse in those without PR. Left ventricular volumes and ejection fraction were normal in both groups but longitudinal function showed significant impairment. This is consistent with few reports which document similar impaired resting RV functional parameters, and LV strain ( 27 , 28 ). During exercise, patients with severe pulmonary regurgitation demonstrated worse RV CR by all longitudinal systolic functional measures. This may be explained by the presence of severe volume overload preventing further RV augmentation. The finding is comparable with other reports ( 6 , 29 ). Conversely, we observed better left ventricular CR in those with PR. There are no previous data for comparison. This balance between differential contractile reserve may go some way to explain our key finding that in our cohort despite the presence of RV dilatation and severe PR, there was no difference in exercise performance. At rest we found that only RV functional parameters were associated with exercise capacity, while importantly RV volume and severity of PR were not. Measured during stress, this signal from functional measures was amplified. In addition, LV longitudinal augmentation was also important suggesting a role for left side systolic impairment in the impaired exercise capacity. Combining these in a single model, resulted in two factors, both relating to function, namely the augmentation of left ventricular longitudinal strain (LVGLS) and the augmentation of right ventricular function (FAC) offering the strongest association with VO 2 . The R 2 was .48, implying that is nearly 50% of the variability in VO 2 could be explained by biventricular functional reserve. Our echo results mirror recent data using CPET and magnetic resonance imaging (MRI) where the LV component of functional reserve was identified as a key predictor of exercise performance. In this study, 35 TOF patients were compared with age matched controls, while in our study we confirm these findings in a larger population and extend the observation to patients with and without severe PR, who would fall into a group of patients with guideline based indication for intervention ( 30 ). There is a small but important literature using both echo and MRI at rest and stress linking this back to exercise performance. Our results are broadly consistent with many studies who have similarly failed to show such associations between severity of PR, RV volume with functional capacity using MRI ( 30 , 31 ), but not with those who showing a positive correlations with RV volume using echocardiography ( 32 ) and MRI ( 6 , 33 , 34 ). These studies are either older studies with smaller cohort size ( 32 ), higher proportion of patients with RVOTO ( 34 ), or their cohort contained a low proportion of patients with severe PR ( 6 , 33 ). Our prospective approach combining coincident investigations make our findings robust. Study limitations This study was limited by the echocardiographic assessment of right ventricular function, volume, and the degree of PR, which is less precise and reproducible than by cardiac magnetic resonance. We excluded patients with intermediate severity of pulmonary regurgitation. We specifically did not address the issue of long-term RV remodeling, RV-PA coupling (because of our inability to reliably measure PA systolic pressure), and arrhythmic potential which represent an alternative reason to undertake intervention to reduced PR. A significant proportion of the control group had undergone previous corrective procedures and the preceding PR might have influence on RV and LV function. Exercise assessment was performed on a semi-supine bike, and this may affect venous return and RV functional parameters. Conclusions Despite a marked reduction in VO 2 in patients with rTOF, the presence of severe PR does not seem to affect VO 2 peak or any other objective measure of exercise function. Given that current indications for surgery or percutaneous intervention in this population are largely based around either symptoms and/or RV volume overload, and in the absence of randomised evidence, our data suggest there is a need to explore the incorporation of functional parameters in clinical decision making and consider other approaches targeting both right and left ventricular performance to optimise symptomatic outcomes. Abbreviations CPET= cardiopulmonary exercise test PR= pulmonary regurgitation VO 2 peak (ml/min) = peak absolute maximum oxygen uptake CR= contractile reserve ΔFAC= contractile reserve of fractional area change ΔLVGLS= contractile reserve of left ventricular global longitudinal strain Declarations Acknowledgments Funding: No external funding. Conflict of interest: The authors declare no conflict of interest. Ethical Approval/ Consent to participate The protocol, informed consent form, participant information sheet and all the study documents were approved by the Health Research Authority (HRA)-Queen Square Research Ethics Committee (Clinical Trial REC Number, 18/LO/0092). All subjects provided written informed consent to participate in the study. IRAS ID is 232328, and the registration date is 16.02.2018. Consent for publication Not applicable References Gerrah R, Turner ME, Gottlieb D, Quaegebeur JM, Bacha EJPc. Repair of tetralogy of Fallot in children less than 4 kg body weight. Pediatric cardiology ;36(7):1344-9. Ternestedt B-M, Wall K, Oddsson H, Riesenfeld T, Groth I, Schollin JJPc. Quality of life 20 and 30 years after surgery in patients operated on for tetralogy of Fallot and for atrial septal defect. Pediatric cardiology;22(2):128-32. Baumgartner H, De Backer J, Babu-Narayan SV, Budts W, Chessa M, Diller G-P, et al. 2020 ESC Guidelines for the management of adult congenital heart disease: The Task Force for the management of adult congenital heart disease of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Adult Congenital Heart Disease (ISACHD). European heart journal;42(6):563-645. Khairy P, Aboulhosn J, Gurvitz MZ, Opotowsky AR, Mongeon Fo-P, Kay J, et al. Arrhythmia burden in adults with surgically repaired tetralogy of Fallot: a multi-institutional study. Circulation;122(9):868-75. Wijesekera VA, Raju R, Precious B, Berger AJ, Kiess MC, Leipsic JA, et al. Sequential right and left ventricular assessment in posttetralogy of Fallot patients with significant pulmonary regurgitation. Congenital Heart Disease;11(6):606-14. Dłużniewska N, Podolec P, Miszalski-Jamka T, Krupiński M, Banyś P, Urbańczyk M, et al. Effect of ventricular function and volumes on exercise capacity in adults with repaired Tetralogy of Fallot. Indian heart journal;70(1):87-92. Fernandes FP, Manlhiot C, Roche SL, Grosse-Wortmann L, Slorach C, McCrindle BW, et al. Impaired left ventricular myocardial mechanics and their relation to pulmonary regurgitation, right ventricular enlargement and exercise capacity in asymptomatic children after repair of tetralogy of Fallot. Journal of the American Society of Echocardiography;25(5):494-503. Van den Eynde J, Sá MPB, Vervoort D, Roever L, Meyns B, Budts W, et al. Pulmonary valve replacement in tetralogy of Fallot: an updated meta-analysis. 2022;113(3):1036-46. Harkness A, Ring L, Augustine DX, Oxborough D, Robinson S, Sharma VJEr, et al. Normal reference intervals for cardiac dimensions and function for use in echocardiographic practice: a guideline from the British Society of Echocardiography. Echo research Journal;7(1):G1-G18. Nyberg J, Jakobsen EO, Østvik A, Holte E, Stølen S, Lovstakken L, et al. Echocardiographic reference ranges of global longitudinal strain for all cardiac chambers using guideline-directed dedicated views. 2023;16(12):1516-31. Wang TKM, Grimm RA, Rodriguez LL, Collier P, Griffin BP, Popović ZBJPO. Defining the reference range for right ventricular systolic strain by echocardiography in healthy subjects: a meta-analysis. 2021;16(8):e0256547. Dandel M, Hetzer RJIjoc. Echocardiographic strain and strain rate imaging—clinical applications. International journal of cardiology;132(1):11-24. Members C, Gibbons RJ, Balady GJ, Timothy Bricker J, Chaitman BR, Fletcher GF, et al. ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). 2002;106(14):1883-92. Glaab T, Taube CJRr. Practical guide to cardiopulmonary exercise testing in adults. 2022;23(1):9. Wasserman K, Hansen J, Sue D, Stringer W, Whipp BJPoEeT, Pathophysiology II, et al. Changes in bloo d gases and pH during exercise. 2005:66-75. Bhatt SM, Elci OU, Wang Y, Goldmuntz E, McBride M, Paridon S, et al. Determinants of exercise performance in children and adolescents with repaired tetralogy of Fallot using stress echocardiography. Pediatric cardiology;40(1):71-8. Buys R, Cornelissen V, Van De Bruaene A, Stevens A, Coeckelberghs E, Onkelinx S, et al. Measures of exercise capacity in adults with congenital heart disease. International journal of cardiology;153(1):26-30. Hock J, Häcker A-L, Reiner B, Oberhoffer R, Hager A, Ewert P, et al. Functional outcome in contemporary children and young adults with tetralogy of Fallot after repair. Journal Archives of disease in childhood;104(2):129-33. Alborikan S, Pandya B, Von Klemperer K, Walker F, Cullen S, Badiani S, et al. Cardiopulmonary Exercise Test (CPET) in patients with repaired Tetralogy of Fallot (rTOF); A systematic review. International Journal of Cardiology Congenital Heart Disease;1:100050. Egidy Assenza G, Krieger EV, Baumgartner H, Cupido B, Dimopoulos K, Louis C, et al. AHA/ACC vs ESC guidelines for management of adults with congenital heart disease: JACC Guideline Comparison. 2021;78(19):1904-18. Dragulescu A, Friedberg MK, Grosse-Wortmann L, Redington A, Mertens LJJotASoE. Effect of chronic right ventricular volume overload on ventricular interaction in patients after tetralogy of Fallot repair. Journal of the American Society of Echocardiography;27(8):896-902. Apostolopoulou SC, Laskari CV, Tsoutsinos A, Rammos SJTijoci. Doppler tissue imaging evaluation of right ventricular function at rest and during dobutamine infusion in patients after repair of tetralogy of Fallot. The international journal of cardiovascular imaging;23(1):25-31. Warnes CA, Williams RG, Bashore TM, Child JS, Connolly HM, Dearani JA, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: a report of the american college of cardiology/american heart association task force on practice guidelines (writing committee to develop guidelines on the management of adults with congenital heart disease) developed in collaboration with the american society of echocardiography, heart rhythm society, international society for adult congenital heart disease, society for cardiovascular angiography and interventions, and society of thoracic surgeons. Journal of the American College of Cardiology;52(23):e143-e263. Geva T, Sandweiss BM, Gauvreau K, Lock JE, Powell AJJJotACoC. Factors associated with impaired clinical status in long-term survivors of tetralogy of Fallot repair evaluated by magnetic resonance imaging. Journal of the American College of Cardiology;43(6):1068-74. Müller J, Hager A, Diller G-P, Derrick G, Buys R, Dubowy K-O, et al. Peak oxygen uptake, ventilatory efficiency and QRS-duration predict event free survival in patients late after surgical repair of tetralogy of Fallot. International journal of cardiology;196:158-64. Khoo NS, Young A, Occleshaw C, Cowan B, Zeng IS, Gentles TLJJotASoE. Assessments of right ventricular volume and function using three-dimensional echocardiography in older children and adults with congenital heart disease: comparison with cardiac magnetic resonance imaging. Journal of the American Society of Echocardiography;22(11):1279-88. Davlouros PA, Kilner PJ, Hornung TS, Li W, Francis JM, Moon JC, et al. Right ventricular function in adults with repaired tetralogy of Fallot assessed with cardiovascular magnetic resonance imaging: detrimental role of right ventricular outflow aneurysms or akinesia and adverse right-to-left ventricular interaction. 2002;40(11):2044-52. Tzemos N, Harris L, Carasso S, Dos Subira L, Greutmann M, Provost Y, et al. Adverse left ventricular mechanics in adults with repaired tetralogy of Fallot. The American journal of cardiology;103(3):420-5. Yazaki K, Takahashi K, Kobayashi M, Yamada M, Iso T, Akimoto S, et al. Exercise echocardiography demonstrates potential myocardial damage in patients with repaired tetralogy of Fallot using layer-specific strain analysis. Cardiology in the Young;30(5):710-6. Steinmetz M, Stümpfig T, Seehase M, Schuster A, Kowallick J, Müller M, et al. Impaired exercise tolerance in repaired tetralogy of fallot is associated with impaired biventricular contractile reserve: an exercise-stress real-time cardiovascular magnetic resonance study. Circulation: Cardiovascular Imaging;14(8):e011823. Meadows J, Powell AJ, Geva T, Dorfman A, Gauvreau K, Rhodes JJTAjoc. Cardiac magnetic resonance imaging correlates of exercise capacity in patients with surgically repaired tetralogy of Fallot. American journal of cardiology;100(9):1446-50. Marx GR, Hicks RW, Allen HD, Goldberg SJJTAjoc. Noninvasive assessment of hemodynamic responses to exercise in pulmonary regurgitation after operations to correct pulmonary outflow obstruction. The American journal of cardiology;61(8):595-601. Giardini A, Specchia S, Coutsoumbas G, Donti A, Formigari R, Fattori R, et al. Impact of pulmonary regurgitation and right ventricular dysfunction on oxygen uptake recovery kinetics in repaired tetralogy of Fallot. European journal of heart failure;8(7):736-43. Freling HG, Willems TP, van Melle JP, van Slooten YJ, Bartelds B, Berger RM, et al. Effect of right ventricular outflow tract obstruction on right ventricular volumes and exercise capacity in patients with repaired tetralogy of fallot. The American journal of cardiology;113(4):719-23. Additional Declarations No competing interests reported. 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18:53:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5342548/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5342548/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":71625395,"identity":"d2255b5c-1642-491a-a555-1656ff41658d","added_by":"auto","created_at":"2024-12-17 08:48:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":32841,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Absolute difference in VO\u003csub\u003e2 \u003c/sub\u003e(ml/min), (b) OUES (ml/min/l/min), and (c) VE/VCO2 slope between two groups.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5342548/v1/e2e3fe64b733dede3ad80c3c.png"},{"id":71625396,"identity":"bdacf7b2-a513-4778-b2ce-15e6f75c04d3","added_by":"auto","created_at":"2024-12-17 08:48:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":65062,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plots of the main determinants of peak VO\u003csub\u003e2\u003c/sub\u003e (ml/min) (RV/LV contractile reserve parameters, ΔFAC and ΔLVGLS).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5342548/v1/e146a5444d01806ef9a3a9bb.png"},{"id":79553566,"identity":"5b169767-f809-41e8-9fb0-3e24f6378210","added_by":"auto","created_at":"2025-03-31 07:01:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1796607,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5342548/v1/de09a469-37da-4f53-b7bc-3ff7c316e404.pdf"},{"id":71625397,"identity":"9b65c3b8-5298-4171-86f9-64da2a2b658d","added_by":"auto","created_at":"2024-12-17 08:48:20","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":369944,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarydata2024.docx","url":"https://assets-eu.researchsquare.com/files/rs-5342548/v1/8ea39d71533ad3ce859cb315.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eEchocardiographic Determinants of Oxygen Uptake During Exercise in Patients with repaired Tetralogy of Fallot and Severe Pulmonary Regurgitation \u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChronic pulmonary regurgitation (PR) remains the most common hemodynamic complication in adult patients with repaired Tetralogy of Fallot (rTOF) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Current guidance supports intervention on the pulmonary valve where regurgitation is severe and the patient experiences symptoms (Class I), and progressive right ventricular (RV) dilatation (Class IIa) (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Despite this, the precise source of progressive functional limitation in TOF is not fully established (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eLeft and right ventricular performance (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) as well as physical deconditioning may also be important (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). This matters in predicting the likely symptomatic benefit from intervention. Previous reports have demonstrated only a limited objective symptomatic benefit for reintervention on the pulmonary valve in this circumstance (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In this prospective cohort study, we hypothesised that more complex mechanisms than the presence of severe PR would be responsible for exercise limitation. To test this, we evaluated patients with rTOF and severe PR, comparing them to a group of patients with no, or negligible PR to establish which echocardiographic parameters were most strongly associated with oxygen uptake (VO\u003csub\u003e2\u003c/sub\u003e peak) and other objective markers of exercise performance.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and population\u003c/h2\u003e \u003cp\u003eWe prospectively recruited adult patients with severe PR after previous TOF repair and a control group with previous TOF repair and negligible or absent PR. Inclusion criteria were 1) diagnosis of repaired TOF; 2) NYHA status less than III; The presence of severe PR was determined by integrated echocardiographic criteria. All patients also underwent clinical cardiac MRI to confirm the diagnosis and the absence of ancillary lesions. Exclusion criteria included significant pulmonary stenosis, right ventricular outflow tract (RVOT) obstruction, severe left ventricular outflow obstruction, RV-Pulmonary artery conduit, ventricular arrhythmias, pacemaker, significant pulmonary hypertension, inability to exercise on the exercise bicycle and poor acoustic windows.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEchocardiography\u003c/h3\u003e\n\u003cp\u003eEchocardiography was performed using a VIVID E95 (Vingmed-General Electric, Horten, Norway) ultrasound platform. Standard 2D, M-mode, colour Doppler, pulsed, continuous wave and colour tissue Doppler were performed according to British Society of Echocardiography guidelines (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). In order to facilitate strain analyses, a frame rate was selected between 35 and 70 frames per second. For 3 dimensional LV and RV analyses, a full volume chamber focused single beat acquisitions were stored with a frame rate not less than 30 (Hz) during end-expiratory breath-hold (utilizing multibeat acquisition when required). Normal reference ranges were taken from a range of contemporary sources (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eStrain analysis was performed offline on the GE Echopac workstation. For the LV, a region of interest was defined in three apical views creating 17 individual regions of interest for regional strain analysis. Individual strain curves were generated for each individual segment, and end systole was defined by aortic valve closure in the 3-chamber view. The GLS was defined as the average of all 17 segments at end systole. For the RV, a similar region of interest was established from the basal septum to the RV apex and then to the tricuspid annulus. The RV was segmented into 3 septal segments and 3 free wall segments. The global RV global longitudinal strain (RV GLS) was the average of all segments while the free wall strain was measured in 3 segments only. All tracking was confirmed manually and in this study we only used the longitudinal component of cardiac function (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eExercise echocardiographic tests were undertaken following a specific image acquisition protocol (Appendix A, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Imaging was undertaken at baseline and at low intensity exercise (defined as 65\u0026ndash;75% peak age predicted heart rate). Peak exercise acquisitions were taken after the respiratory exchange ratio (RER) was \u0026gt;\u0026thinsp;1.0. This provided a standardised heart rate independent point beyond ventilatory threshold but with sufficient remaining exercise time to allow measurements to be made during high intensity exercise. The following measures were made at baseline and peak stages including RV and LV size function, pulmonary regurgitation and 3D volume. Strain imaging was not undertaken at high intensity exercise because of the effect of heart rate on analysis algorithms (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eContractile reserve (CR) was the percentage increase in each parameter during exercise at either peak or low intensity exercise depending on the known behavior of the parameter (e.g parameters which plateau or where there are specific software limitations such as GLS).\u003c/p\u003e\n\u003ch3\u003eCardiopulmonary exercise testing (CPET)\u003c/h3\u003e\n\u003cp\u003eCardio pulmonary exercise testing was performed according to exercise testing protocol (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) on a semi-recumbent tilting cycle ergometer (ERG 911 S/L, Schiller, Switzerland). Maximum oxygen uptake (V̇O\u003csub\u003e2\u003c/sub\u003e peak) was continuously measured using a calibrated breath-by-breath analyzer (Cosmed Quark CPET, Rome, Italy). Peak oxygen consumption (V̇O\u003csub\u003e2\u003c/sub\u003e), carbon dioxide production (VCO\u003csub\u003e2\u003c/sub\u003e), and minute ventilation (VE) were acquired breath-by‐breath and averaged over a 10‐second interval. Exercise protocols were individually determined based on the patient functional status with work rate (5-20W) increased every minute until voluntary exhaustion. Heart rate (HR), blood pressure, and oxygen saturation were monitored throughout. A RER\u0026thinsp;\u0026gt;\u0026thinsp;1 was used to indicate adequate effort. peak V̇O\u003csub\u003e2\u003c/sub\u003e was the highest value from an average of 30 seconds during the final stage of the exercise test. Oxygen Uptake Efficiency Slope (OUES) defined as the regression slope between V̇O\u003csub\u003e2\u003c/sub\u003e and Log minute ventilation (Ve), and ventilatory efficiency defined as the ratio of VE/VCO\u003csub\u003e2\u003c/sub\u003e expressed as the slope function between VT and before respiratory compensation point. Peak V̇O\u003csub\u003e2\u003c/sub\u003e values less than 84%, VE/VCO2\u0026thinsp;\u0026gt;\u0026thinsp;34, and an OUES\u0026thinsp;\u0026lt;\u0026thinsp;80%, were considered abnormal (14, 15).\u003c/p\u003e\n\u003ch3\u003eStatistical analyses\u003c/h3\u003e\n\u003cp\u003eVO\u003csub\u003e2\u003c/sub\u003e peak was the primary end point for the study. We estimated a sample size of 25 in the cases and controls and this would permit the detection of a 30% (clinically meaningful difference between the groups). We recruited 2:1 in favor of severe PR to permit the assessment of clinical and echocardiographic predictors of exercise performance in this group. Continuous variables were presented as mean and standard deviations (SD). Student\u0026rsquo;s t tests were performed for all parameters. Univariate correlation analyses were constructed to determine relationships between hemodynamic echocardiographic and exercise parameters. Multivariate regression analysis model was constructed for absolute VO\u003csub\u003e2\u003c/sub\u003e (ml/min) for this regression PR was treated as a categorical variable. All statistical analyses were performed using IBM SPSS statistics version 27 (IBMCorp, London, United Kingdom). The study was approved by the Health Research Authority-Queen Square Research Ethics Committee (18/LO/0092).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e120 patients were recruited, of whom 20 patients were excluded due to severity of pulmonary stenosis, inability to exercise or right ventricular arrythmia, leaving 100 patients, 60 with severe PR and 40 controls. Baseline characteristics are presented in table 1. The PR group was older (35\u0026plusmn;13 vs 33\u0026plusmn;11, years, p\u0026lt;0.05) and were marginally more frequently male. PR group also had higher frequency of transannular patch (TAP) (85 vs 68, %, p\u0026lt;0.05) as the primary operation. 9 patients with PR (15%) had previous reintervention with surgical pulmonary valve replacement, compared to 21 patients (53%) in the no PR subjects. The average of individualised exercise protocols was 15w (range 5-20W). A RER of \u0026gt;1.01 was achieved in 97 patients, with a mean value of 1.2\u0026plusmn;.1 in both groups. The termination of exercise was either due to leg fatigue, shortness of breath or general fatigue.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eBaseline charactristics.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.9084%;\"\u003e\n \u003cp\u003eBaseline characteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSevere PR group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo PR group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.8924%;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.9084%;\"\u003e\n \u003cp\u003eAge (yrs)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Sex\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e35 \u0026plusmn;13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e33\u0026plusmn;11\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.8924%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.9084%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Male\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e31 (52%)\u003c/p\u003e\n \u003cp\u003e29 (48%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e19 (48%)\u003c/p\u003e\n \u003cp\u003e21(52%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.8924%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.9084%;\"\u003e\n \u003cp\u003eHeight (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e166\u0026plusmn;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;169\u0026plusmn;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.8924%;\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.9084%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Weight (kg)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e71\u0026plusmn;16\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e73\u0026plusmn;14\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.8924%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.9084%;\"\u003e\n \u003cp\u003eBMI (Kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e25\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e26\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.8924%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.9084%;\"\u003e\n \u003cp\u003eORS duration (ms)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e153\u0026plusmn;20\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e150\u0026plusmn;22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.8924%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 22.9084%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of surgery\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eTAP\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eOther RVOT intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e51 (85%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0996%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27 (68%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 13 (32%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.8924%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;BMI=body mass index; TAP= transannular patch. * Bold values indicate significant level (p\u0026lt;.05); NS=non-significant.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere was no difference in objective exercise performance between patients with and without severe PR. The average exercise time was 10\u0026plusmn;2 minutes in the PR group and 9\u0026plusmn;1 minutes in the no PR group (P\u0026gt;0.05) with similar maximal workload achieved (150\u0026plusmn;55 vs 151\u0026plusmn;49 W, p\u0026gt;0.05) (Table2). These results were mirrored in the metabolic exercise testing where VO\u003csub\u003e2\u003c/sub\u003e (1695\u0026plusmn;627, ml/min vs 1744\u0026plusmn;521, ml/min, p\u0026gt;0.05) was similar between the two groups (Figure 1a). 48 patients (80%) fell below the normal range for predicted VO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ein the PR group, compared to 28 patients (70%) in the control group (p\u0026gt;0.05, Table 2).\u0026nbsp;We also demonstrated no difference across the pre-specified submaximal measure of exercise performance including OUES (1885\u0026plusmn;722 vs 1869\u0026plusmn;543, ml/min/l/min, p\u0026gt;0.05), and ventilatory efficiency where the VE/VCO\u003csub\u003e2\u003c/sub\u003e slope was not different (26\u0026plusmn;4 vs 25\u0026plusmn;5, p\u0026gt;0.05) (Table 2, Figure 1b and c).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eCardiopulmonary exercise performance and the difference between severe PR and no PR groups.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"102%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCPET parameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSevere\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;PR group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo PR group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;P value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMax effort measures\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eExercise duration (min)\u003c/p\u003e\n \u003cp\u003eExercise protocol (w)\u003c/p\u003e\n \u003cp\u003ePeak oxygen uptake VO\u003csub\u003e2\u003c/sub\u003e (ml/min)\u003c/p\u003e\n \u003cp\u003ePeak oxygen consumption VO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003e(ml/kg/min)\u003c/p\u003e\n \u003cp\u003ePeak percent of predicted VO\u003csub\u003e2\u003c/sub\u003e (%)\u003c/p\u003e\n \u003cp\u003eImpaired peak percent of predicted VO\u003csub\u003e2\u003c/sub\u003e (%)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePeak RER\u003c/p\u003e\n \u003cp\u003ePeak HR (beat/min)\u003c/p\u003e\n \u003cp\u003ePredicted HR (%)\u003c/p\u003e\n \u003cp\u003eSBP at peak (mmHg)\u003c/p\u003e\n \u003cp\u003ePeak workload (W)\u003c/p\u003e\n \u003cp\u003ePeak workload predicted (%)\u003c/p\u003e\n \u003cp\u003eO\u003csub\u003e2\u003c/sub\u003e saturation (%)\u003c/p\u003e\n \u003cp\u003ePeak O\u003csub\u003e2\u003c/sub\u003e pulse (ml/beat)\u003c/p\u003e\n \u003cp\u003ePredicted O\u003csub\u003e2\u003c/sub\u003e pulse (%)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003ePeak VE/VCO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10\u0026plusmn;2\u003c/p\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003cp\u003e1695\u0026plusmn;627\u003c/p\u003e\n \u003cp\u003e24\u0026plusmn;7\u003c/p\u003e\n \u003cp\u003e75\u0026plusmn;17\u003c/p\u003e\n \u003cp\u003e67 \u0026plusmn;14\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.2\u0026plusmn;.1\u003c/p\u003e\n \u003cp\u003e150\u0026plusmn;20\u003c/p\u003e\n \u003cp\u003e81\u0026plusmn;10\u003c/p\u003e\n \u003cp\u003e192\u0026plusmn;33\u003c/p\u003e\n \u003cp\u003e150\u0026plusmn;55\u003c/p\u003e\n \u003cp\u003e90\u0026plusmn;29\u003c/p\u003e\n \u003cp\u003e97\u0026plusmn;1\u003c/p\u003e\n \u003cp\u003e11\u0026plusmn;4\u003c/p\u003e\n \u003cp\u003e91\u0026plusmn;18\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 20%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9\u0026plusmn;1\u003c/p\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003cp\u003e1744\u0026plusmn;521\u003c/p\u003e\n \u003cp\u003e25\u0026plusmn;7\u003c/p\u003e\n \u003cp\u003e76\u0026plusmn;17\u003c/p\u003e\n \u003cp\u003e68 \u0026plusmn;11\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.2\u0026plusmn;.1\u003c/p\u003e\n \u003cp\u003e155\u0026plusmn;19\u003c/p\u003e\n \u003cp\u003e84\u0026plusmn;10\u003c/p\u003e\n \u003cp\u003e185\u0026plusmn;26\u003c/p\u003e\n \u003cp\u003e151\u0026plusmn;49\u003c/p\u003e\n \u003cp\u003e88\u0026plusmn;23\u003c/p\u003e\n \u003cp\u003e98\u0026plusmn;1\u003c/p\u003e\n \u003cp\u003e11\u0026plusmn;3\u003c/p\u003e\n \u003cp\u003e92\u0026plusmn;19\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e30\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 48%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSub max effort measures\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eVE/VCO\u003csub\u003e2\u003c/sub\u003e at AT\u003c/p\u003e\n \u003cp\u003eVE/VCO\u003csub\u003e2\u003c/sub\u003e slope\u003c/p\u003e\n \u003cp\u003eOUES (ml/min/l/min)\u003c/p\u003e\n \u003cp\u003ePredicted OUES (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28 \u0026plusmn;3\u003c/p\u003e\n \u003cp\u003e26\u0026plusmn;4\u003c/p\u003e\n \u003cp\u003e1885\u0026plusmn;722\u003c/p\u003e\n \u003cp\u003e73\u0026plusmn;20\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 20%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e25\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e1869\u0026plusmn;543\u003c/p\u003e\n \u003cp\u003e74\u0026plusmn;18\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;NS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eVO\u003csub\u003e2\u003c/sub\u003e=peak absolute maximum oxygen uptake in absolute (ml/min), relative (ml/kg/min), percent of predicted (%); RER=respiratory exchange ratio; HR=heart rate; SBP=systolic blood pressure; O\u003csub\u003e2\u003c/sub\u003e pulse=oxygen uptake divided by heart rate peak and predicted; VE/VCO\u003csub\u003e2\u003c/sub\u003e=the\u003cstrong\u003e\u0026nbsp;relationship between minute ventilation and carbon dioxide production at peak, at anaerobic threshold, and slope; OUES=\u003c/strong\u003eOxygen uptake efficiency slope peak and predicted. NS=non-significant.\u003c/p\u003e\n\u003cp\u003eFull echocardiographic dataset is presented in table 3. The PR group had greater RV dimensions and volumes with 73% demonstrating RV diastolic and systolic volumes above the normal range, compared with 28% of controls (Table 3). RV fractional area change was similar in both groups (44\u0026plusmn;6 vs 42\u0026plusmn;6, %, p\u0026gt;0.05, Table 3), but RVGLS and RV global free wall strain (RVGFWS) were generally lower (better function) in the PR group. Right ventricular CR was however lower in the PR group, this was true for velocity augmentation; longitudinal excursion; and RV fractional area change. RVGLS in the PR group increased by 16% compared with 20% in controls (p\u0026lt;0.05) (Table 4). Normal LV volumes were observed in 90% of PR group and in 83% of the no PR group (p\u0026gt;0.05) (Table 3). LVEF and velocity augmentation (LVS) were similar in both groups. LV global longitudinal strain (LVGLS) was not different between groups with a GLS \u0026lt;-20% in 95% and 100% respectively (Table 3). Higher left ventricular longitudinal CR as measured by LVEF, LVS\u0026rsquo; and longitudinal excursion, but not GLS, were observed in the PR group (Table 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e Baseline echocardiographic difference.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"112%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.7083%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline RV parameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSevere PR group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo PR group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.33333%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.7083%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline LV parameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSevere PR group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo PR group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.33333%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.7083%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003e2D Structure and function\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRVD Mid (cm)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRVD Basal (cm)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRVEDA (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRVESA (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFAC (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTAPSE (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRVS\u0026rsquo; (cm/s)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRA (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003ePulmonary Regurgitation\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePR PG (mmHg)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePR PHT (ms)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePR index\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePACT (ms)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDSTVI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTR (mmHg)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePASp (mmHg)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003e3D Volume and function\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRVEDV (ml)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRVEDVI (ml/m\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRVESV (ml)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRVESVI (ml/m\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRVEF (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRVSV (ml/m\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRVSVI (ml/m\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTAPSI (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;FAC (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4\u0026plusmn;.5\u003c/p\u003e\n \u003cp\u003e5\u0026plusmn;.3\u003c/p\u003e\n \u003cp\u003e28\u0026plusmn;6\u003c/p\u003e\n \u003cp\u003e16\u0026plusmn;4\u003c/p\u003e\n \u003cp\u003e43\u0026plusmn;6\u003c/p\u003e\n \u003cp\u003e17\u0026plusmn;3\u003c/p\u003e\n \u003cp\u003e8\u0026plusmn;2\u003c/p\u003e\n \u003cp\u003e19\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22\u0026plusmn;8\u003c/p\u003e\n \u003cp\u003e84\u0026plusmn;22\u003c/p\u003e\n \u003cp\u003e.4\u0026plusmn;.1\u003c/p\u003e\n \u003cp\u003e147\u0026plusmn;27\u003c/p\u003e\n \u003cp\u003e1.2\u0026plusmn;.33\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23\u0026plusmn;10\u003c/p\u003e\n \u003cp\u003e35\u0026plusmn;7\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e179\u0026plusmn;51\u003c/p\u003e\n \u003cp\u003e101\u0026plusmn;26\u003c/p\u003e\n \u003cp\u003e88\u0026plusmn;31\u003c/p\u003e\n \u003cp\u003e50\u0026plusmn;16\u003c/p\u003e\n \u003cp\u003e51\u0026plusmn;7\u003c/p\u003e\n \u003cp\u003e91\u0026plusmn;27\u003c/p\u003e\n \u003cp\u003e51\u0026plusmn;14\u003c/p\u003e\n \u003cp\u003e17\u0026plusmn;3\u003c/p\u003e\n \u003cp\u003e44\u0026plusmn;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.4\u0026plusmn;.5\u003c/p\u003e\n \u003cp\u003e4.1\u0026plusmn;.6\u003c/p\u003e\n \u003cp\u003e22\u0026plusmn;6\u003c/p\u003e\n \u003cp\u003e13\u0026plusmn;4\u003c/p\u003e\n \u003cp\u003e41\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e14\u0026plusmn;4\u003c/p\u003e\n \u003cp\u003e6\u0026plusmn;2\u003c/p\u003e\n \u003cp\u003e17\u0026plusmn;4\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18\u0026plusmn;9\u003c/p\u003e\n \u003cp\u003e32\u0026plusmn;8\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e128\u0026plusmn;30\u003c/p\u003e\n \u003cp\u003e70\u0026plusmn;14\u003c/p\u003e\n \u003cp\u003e67\u0026plusmn;21\u003c/p\u003e\n \u003cp\u003e37\u0026plusmn;10\u003c/p\u003e\n \u003cp\u003e48\u0026plusmn;8\u003c/p\u003e\n \u003cp\u003e62\u0026plusmn;15\u003c/p\u003e\n \u003cp\u003e34\u0026plusmn;8\u003c/p\u003e\n \u003cp\u003e13\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e42\u0026plusmn;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.33333%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.7083%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003e2D Structure and function\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLVEDD (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLVESDD (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLVEF (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMAPSE (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLVS\u0026rsquo; (cm/s)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eE/A\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eE\u0026rsquo; (cm/s)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eE/e\u0026rsquo;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003e3D Volume and function\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLVEDV (ml) \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLVEDVI (ml/m\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLVESV (ml)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLVESVI (ml/m\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLVEF (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLV SV (ml)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLVSVI (ml/m\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCO (l/m)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003e2D Strain\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRVGLS (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRVGFWS (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLVGLS (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38\u0026plusmn;6\u003c/p\u003e\n \u003cp\u003e26\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e58\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e17\u0026plusmn;2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 7\u0026plusmn;3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 1.5\u0026plusmn;.4\u003c/p\u003e\n \u003cp\u003e8\u0026plusmn;2\u003c/p\u003e\n \u003cp\u003e10\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e110\u0026plusmn;29\u003c/p\u003e\n \u003cp\u003e67\u0026plusmn;20\u003c/p\u003e\n \u003cp\u003e46\u0026plusmn;14\u003c/p\u003e\n \u003cp\u003e29\u0026plusmn;13\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;59\u0026plusmn;4\u003c/p\u003e\n \u003cp\u003e64\u0026plusmn;16\u003c/p\u003e\n \u003cp\u003e39\u0026plusmn;13\u003c/p\u003e\n \u003cp\u003e5\u0026plusmn;1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-17\u0026plusmn;3\u003c/p\u003e\n \u003cp\u003e-19\u0026plusmn;3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;-15\u0026plusmn;2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e39\u0026plusmn;8\u003c/p\u003e\n \u003cp\u003e27\u0026plusmn;6\u003c/p\u003e\n \u003cp\u003e59\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e15\u0026plusmn;3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;7\u0026plusmn;6\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;1.3\u0026plusmn;.3\u003c/p\u003e\n \u003cp\u003e6\u0026plusmn;2\u003c/p\u003e\n \u003cp\u003e13\u0026plusmn;4\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e105 \u0026plusmn;13\u003c/p\u003e\n \u003cp\u003e58\u0026plusmn;8\u003c/p\u003e\n \u003cp\u003e44\u0026plusmn;8\u003c/p\u003e\n \u003cp\u003e24\u0026plusmn;4\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;58\u0026plusmn;4\u003c/p\u003e\n \u003cp\u003e55\u0026plusmn;9\u003c/p\u003e\n \u003cp\u003e33\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e4\u0026plusmn;.7\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-15\u0026plusmn;3\u003c/p\u003e\n \u003cp\u003e-17\u0026plusmn;3\u003c/p\u003e\n \u003cp\u003e-15\u0026plusmn;3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.33333%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;NS\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u0026nbsp;\u003c/strong\u003eNS\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eRVD mid=right ventricular mid-size; RVD base=right ventricular basal-size; RVEDA=right ventricular end diastolic area; RVESA=right ventricular end systolic area; FAC=fractional area change; TAPSE=tricuspid annular plane systolic excursion; RVS\u0026rsquo;=right ventricular systolic velocity; RA=right atrium; PR PG=pulmonary regurgitation pressure gradient; PR PHT=pulmonary regurgitation pressure half time; PR index=severe pulmonary regurgitation index; PACT=pulmonary acceleration time; DSTVI=the ratio of diastolic and systolic time-velocity integrals; TR=tricuspid regurgitation; PASp=pulmonary artery systolic pressure; RVEDV=right ventricular end diastolic volume; RVEDVI=indexed right ventricular end diastolic volume; RVESV=right ventricular end systolic volume; RVESVI=indexed right ventricular end systolic volume; RVEF=right ventricular ejection fraction; RVSV=right ventricular stroke volume; RVSVI=indexed right ventricle stroke volume. Bold values indicate significant level (p\u0026lt;0.05); LVEDD=left ventricular end diastolic diameter; ; LVESD=left ventricular end systolic diameter; LVEF=left ventricular ejection fraction; MAPSE=mitral annular systolic excursion; ; LVS\u0026rsquo;= Averag left ventricular systolic velocity; E/A=\u003cstrong\u003er\u003cstrong\u003eatio between E-wave and A-wave; E\u0026rsquo; average= average of septal and lateral early mitral inflow velocity;\u0026nbsp;\u003c/strong\u003e\u003c/strong\u003eE\u003cstrong\u003e/\u003c/strong\u003ee\u0026rsquo;=ratio between early mitral inflow velocity and mitral annular early diastolic velocity; LVEDV=left ventricular end diastolic volume; LVEDVI= indexed left ventricular end diastolic volume; LVESV=left ventricular end systolic volume; LVESVI=indexed left ventricular end systolic volume; LVEF= left ventricular ejection fraction; LVSV=left ventricular stroke volume; LVSVI=indexed left ventricular stroke volume; CO=cardiac output. Bold values indicate significant level (p\u0026lt;0.05); RVGLS=right ventricular global longitudinal strain; RVGFWS=right ventricular global free wall stain; LVGLS=left ventricular global longitudinal strain. Bold values indicate significant level (p\u0026lt;0.05); NS=non-significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4.\u003c/strong\u003e Contractile reserve parameters difference between groups.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"93%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37.1134%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e% of Change from rest to RER \u0026gt;1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFunctional and Volumetric CR parameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7423%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSevere PR group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.6186%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo PR group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5258%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37.1134%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003eRight Ventricle\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026Delta;\u003c/strong\u003eFAC (%)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026Delta;\u003c/strong\u003eTAPSE (%)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026Delta;\u003c/strong\u003eRVS\u0026rsquo; (%)\u003c/p\u003e\n \u003cp\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003eLeft ventricle\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026Delta;\u003c/strong\u003eLVEF (%)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026Delta;\u003c/strong\u003eMAPSE (%)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026Delta;\u003c/strong\u003eLVS\u0026rsquo; average (%)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026Delta;\u003c/strong\u003eLVEDV\u0026nbsp;(%)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026Delta;\u003c/strong\u003e LVEDVI (%)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026Delta;\u003c/strong\u003e LVESV (%)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026Delta;\u003c/strong\u003eLVESVI (ml/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026Delta;\u003c/strong\u003eLVSV (ml)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026Delta;\u003c/strong\u003eLVSVI\u0026nbsp;(ml/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026Delta;\u003c/strong\u003eCO\u003c/p\u003e\n \u003cp\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cu\u003eStrain parameters\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026Delta;RVGLS (%)\u003c/p\u003e\n \u003cp\u003e\u0026Delta;RVGFWS (%)\u003c/p\u003e\n \u003cp\u003e\u0026Delta;LVGLS (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7423%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;20\u0026plusmn;15\u003c/p\u003e\n \u003cp\u003e39\u0026plusmn;28\u003c/p\u003e\n \u003cp\u003e41\u0026plusmn;28\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 26\u0026plusmn;9\u003c/p\u003e\n \u003cp\u003e37\u0026plusmn;17\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;67\u0026plusmn;34\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; -16\u0026plusmn;14\u003c/p\u003e\n \u003cp\u003e-19\u0026plusmn;17\u003c/p\u003e\n \u003cp\u003e-38\u0026plusmn;18\u003c/p\u003e\n \u003cp\u003e-40\u0026plusmn;22\u003c/p\u003e\n \u003cp\u003e3\u0026plusmn;11\u003c/p\u003e\n \u003cp\u003e3\u0026plusmn;14\u003c/p\u003e\n \u003cp\u003e84\u0026plusmn;44\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;16\u0026plusmn;13\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;7\u0026plusmn;6\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;15\u0026plusmn;14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.6186%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 23\u0026plusmn;16\u003c/p\u003e\n \u003cp\u003e42\u0026plusmn;28\u003c/p\u003e\n \u003cp\u003e48\u0026plusmn;20\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;24\u0026plusmn;6\u003c/p\u003e\n \u003cp\u003e33\u0026plusmn;21\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 61\u0026plusmn;28\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; -13\u0026plusmn;8\u003c/p\u003e\n \u003cp\u003e-13\u0026plusmn;9\u003c/p\u003e\n \u003cp\u003e-35\u0026plusmn;13\u003c/p\u003e\n \u003cp\u003e-34\u0026plusmn;13\u003c/p\u003e\n \u003cp\u003e-2\u0026plusmn;2\u003c/p\u003e\n \u003cp\u003e-4\u0026plusmn;8\u003c/p\u003e\n \u003cp\u003e62\u0026plusmn;48\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;20\u0026plusmn;19\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 13\u0026plusmn;12\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 16\u0026plusmn;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5258%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026Delta;FAC=contractile reserve of fractional area change; \u0026Delta;TAPSE=contractile reserve of tricuspid annular plane systolic excursion; \u0026Delta;RVS\u0026rsquo;=contractile reserve of right ventricular systolic velocity; \u0026Delta;RVEF=contractile reserve of right ventricle ejection fraction; \u0026Delta;RVSV= contractile reserve of right ventricular stroke volume; \u0026Delta;RVSVI= contractile reserve of indexed right ventricle stroke volume; \u0026Delta;MAPSE=contractile reserve of mitral annular systolic excursion; \u0026Delta;LVS\u0026rsquo;=contractile reserve of left ventricular systolic velocity; \u0026Delta;LVEDV=contractile reserve of left ventricular end diastolic volume; \u0026Delta;LVEDVI=contractile reserve of indexed left ventricular end diastolic volume; \u0026Delta;LVESV=contractile reserve of left ventricular end systolic volume; \u0026Delta;LVESVI=contractile reserve of indexed left ventricular end systolic volume; \u0026Delta;LVSV=contractile reserve of left ventricular stroke volume; \u0026Delta;LVSVI=contractile reserve of indexed left ventricular stroke volume; \u0026Delta;CO=contractile reserve of cardiac output. Bold values indicate significant level (p\u0026lt;0.05); \u0026Delta;RVGLS=contractile reserve of right ventricular global longitudinal strain; \u0026Delta;RVGFWS=contractile reserve of right ventricular global free wall stain; \u0026Delta;LVGLS=contractile reserve of left ventricular global longitudinal strain. Bold values indicate significant level (p\u0026lt;0.05); NS=non-significant.\u003c/p\u003e\n\u003cp\u003eNone of the quantification parameters of which describe pulmonary regurgitation were correlated with peak oxygen consumption (Table 5). Across both groups, resting RV parameters including FAC, RV stroke volume (RVSV) and RVGFWS were associated with peak VO\u003csub\u003e2\u003c/sub\u003e. Similarly, some resting parameters of LV systolic and diastolic function showed correlation with VO\u003csub\u003e2\u003c/sub\u003e.\u0026nbsp;In multivariate modelling change in left ventricular long axis reserve (expressed as change in GLS) (r=-.55, p\u0026lt;0.05), and\u0026nbsp;RV fractional area change\u0026nbsp;(r=.45, p\u0026lt;0.05) were the most important associations with peak oxygen consumption (model R\u003csup\u003e2\u003c/sup\u003e= .48, p\u0026lt;0.001, Table 5, Figure 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003cstrong\u003eTable 5.\u003c/strong\u003e Determinants of peak absolute VO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003e(ml/min).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"567\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN=100\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 21.7314%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003e(ml/min)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eContractile reserve \u0026Delta;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(VO\u003csub\u003e2\u003c/sub\u003e, ml/min) PR (0/1)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u003cstrong\u003eR\u003csup\u003e2\u003c/sup\u003e= .48, p\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLeft ventricle\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e2D analyses\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(R)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeak stress\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(R)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003e2DLVEF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.49*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.45\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.56\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eLVS\u0026rsquo; average, cm/s\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.35*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.22\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.31\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eMAPSE, mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eE/e\u0026rsquo;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-.32*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e-.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eLVGLS (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-.30*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-.50**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-.55\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.40\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3D Analyses\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eLVEDV, ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eLVEDVI, ml/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eLVESV, ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e-.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e-.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eLVESVI, ml/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eLVSV, ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eLVSVI, ml/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.27*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003eNS\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRight ventricle\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e2D analyses\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eRVD mid (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e-.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eRVD basal (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e-.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eTAPSE (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e-0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.27**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eFAC (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.37*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.39*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.40*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.45\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.35\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eRVS\u0026rsquo; (cm/s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e-.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eRVGLS (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eRVGFWS (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.46**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.89399%;\"\u003e\n \u003cp\u003e.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3D Analyses\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eRVEDV (ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e-.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eRVEDVI (ml/m2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e-.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eRVESV (ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e-.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eRVESVI (ml/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e-.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eRVEF (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e-55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eRVSV (ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.39*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eRVSVI (ml/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePulmonary regurgitation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003ePR PG (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003ePR Index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003ePHT (ms)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.0283%;\"\u003e\n \u003cp\u003eDSTVI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0707%;\"\u003e\n \u003cp\u003e-.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6608%;\"\u003e\n \u003cp\u003e.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.9576%;\"\u003e\n \u003cp\u003e-.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7774%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 19.788%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.71731%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eLVEF=left ventricular ejection fraction; MAPSE=mitral annular systolic excursion; ; LVS\u0026rsquo;=left ventricular systolic velocity; E/e\u0026rsquo;=ratio between early mitral inflow velocity and mitral annular early diastolic velocity; LVEDV=left ventricular end diastolic volume; LVEDVI=indexed left ventricular end diastolic volume; LVESV=left ventricular end systolic volume; LVESVI=indexed left ventricular end systolic volume; LVEF=left ventricular ejection fraction; LVSV=left ventricular stroke volume; LVSVI=indexed left ventricular stroke; RV mid=right ventricular mid-size; RV base=right ventricular basal-size;\u0026nbsp;TAPSE=tricuspid annular plane systolic excursion; FAC=fractional area change; RVS\u0026rsquo;=right ventricular systolic velocity; RVEDV=right ventricular end diastolic volume; RVEDVI= indexed right ventricular end diastolic volume; RVESV=right ventricular end systolic volume; RVESVI=indexed right ventricular end systolic volume; RVEF=right ventricular ejection fraction; RVSV=right ventricular stroke volume; RVSVI= indexed right ventricle stroke volume.\u0026nbsp;Bold values indicate significant level (p\u0026lt;0.05);\u0026nbsp;PG=pulmonary regurgitation pressure gradient; PR index=severe pulmonary regurgitation index; RVGLS=right ventricular global longitudinal strain; RVGFWS=right ventricular global free wall stain; LVGLS=left ventricular global longitudinal strain. \u0026Delta;FAC=contractile reserve of\u0026nbsp;fractional area change; \u0026Delta;LVGLS=contractile reserve of\u0026nbsp;left ventricular global longitudinal strain.\u0026nbsp;Bold values indicate significant level (p\u0026lt;0.05).\u003c/p\u003e\n"},{"header":"Discussion","content":"\u003cp\u003eWe have demonstrated that in patients with rTOF those with severe pulmonary regurgitation have the same objective exercise capacity as those with only mild or no valve incompetence despite evidence of RV remodeling and dilatation. Exploratory echocardiographic analyses suggest that the functional parameters of both the right and left ventricles, especially under stress conditions, rather than the presence of PR or RV remodeling, are the most important, accounting together for nearly 50% of the variability in VO\u003csub\u003e2\u003c/sub\u003e.\u003c/p\u003e \u003cp\u003eThe functional limitations we observed is in keeping with most previous studies (\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), and with a recent systematic review that showed an overall mild exercise intolerance with a peak predicted VO\u003csub\u003e2\u003c/sub\u003e of 68% ​\u0026plusmn; ​2.8 (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Many factors including the choice of surgical approach (especially transannular patch) (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), latent left ventricular dysfunction, often with a preserved EF (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), the effect of ventricular interdependency (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), and restrictive RV physiology (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) may also play an important role over and above a simple regurgitation / right ventricular volume model. Current guidelines for intervention are however based on observational data and the precise balance between volumes and function as predictors of exercise ability is less well understood (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this study as expected, there was a marked reduction in exercise capacity across all patients, however patients with severe PR and patients with mild or no PR had no difference in oxygen uptake (VO\u003csub\u003e2\u003c/sub\u003e), Oxygen Uptake Efficiency Slope (OUES) or ventilatory efficiency (VE/VCO2 slope) despite being well balanced and without major confounders. Other than a slight difference in age and the frequency of TAP surgery, there were no substantial confounders. While there is often an observed disconnect between the perception of the symptom of breathlessness and VO\u003csub\u003e2\u003c/sub\u003e max (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e), our data also shows the same finding for submaximal effort parameters (which allows for those subjects who were unable to reach RER\u0026thinsp;\u0026gt;\u0026thinsp;1.1), and ventilatory efficiency which is more closely linked to the perception of breathlessness (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAs expected, the right ventricular myocardial volumes were larger in the severe PR group consistent with multiple previous investigations(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). RV longitudinal functional abnormalities were observed in both groups and, interestingly the measures of RV function were slightly worse in those without PR. Left ventricular volumes and ejection fraction were normal in both groups but longitudinal function showed significant impairment. This is consistent with few reports which document similar impaired resting RV functional parameters, and LV strain (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDuring exercise, patients with severe pulmonary regurgitation demonstrated worse RV CR by all longitudinal systolic functional measures. This may be explained by the presence of severe volume overload preventing further RV augmentation. The finding is comparable with other reports (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Conversely, we observed better left ventricular CR in those with PR. There are no previous data for comparison. This balance between differential contractile reserve may go some way to explain our key finding that in our cohort despite the presence of RV dilatation and severe PR, there was no difference in exercise performance.\u003c/p\u003e \u003cp\u003eAt rest we found that only RV functional parameters were associated with exercise capacity, while importantly RV volume and severity of PR were not. Measured during stress, this signal from functional measures was amplified. In addition, LV longitudinal augmentation was also important suggesting a role for left side systolic impairment in the impaired exercise capacity. Combining these in a single model, resulted in two factors, both relating to function, namely the augmentation of left ventricular longitudinal strain (LVGLS) and the augmentation of right ventricular function (FAC) offering the strongest association with VO\u003csub\u003e2\u003c/sub\u003e. The R\u003csup\u003e2\u003c/sup\u003e was .48, implying that is nearly 50% of the variability in VO\u003csub\u003e2\u003c/sub\u003e could be explained by biventricular functional reserve.\u003c/p\u003e \u003cp\u003eOur echo results mirror recent data using CPET and magnetic resonance imaging (MRI) where the LV component of functional reserve was identified as a key predictor of exercise performance. In this study, 35 TOF patients were compared with age matched controls, while in our study we confirm these findings in a larger population and extend the observation to patients with and without severe PR, who would fall into a group of patients with guideline based indication for intervention (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). There is a small but important literature using both echo and MRI at rest and stress linking this back to exercise performance. Our results are broadly consistent with many studies who have similarly failed to show such associations between severity of PR, RV volume with functional capacity using MRI (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), but not with those who showing a positive correlations with RV volume using echocardiography (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) and MRI (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). These studies are either older studies with smaller cohort size (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e), higher proportion of patients with RVOTO (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e), or their cohort contained a low proportion of patients with severe PR (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Our prospective approach combining coincident investigations make our findings robust.\u003c/p\u003e\n\u003ch3\u003eStudy limitations\u003c/h3\u003e\n\u003cp\u003eThis study was limited by the echocardiographic assessment of right ventricular function, volume, and the degree of PR, which is less precise and reproducible than by cardiac magnetic resonance. We excluded patients with intermediate severity of pulmonary regurgitation. We specifically did not address the issue of long-term RV remodeling, RV-PA coupling (because of our inability to reliably measure PA systolic pressure), and arrhythmic potential which represent an alternative reason to undertake intervention to reduced PR. A significant proportion of the control group had undergone previous corrective procedures and the preceding PR might have influence on RV and LV function. Exercise assessment was performed on a semi-supine bike, and this may affect venous return and RV functional parameters.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eDespite a marked reduction in VO\u003csub\u003e2\u003c/sub\u003e in patients with rTOF, the presence of severe PR does not seem to affect VO\u003csub\u003e2\u003c/sub\u003e peak or any other objective measure of exercise function. Given that current indications for surgery or percutaneous intervention in this population are largely based around either symptoms and/or RV volume overload, and in the absence of randomised evidence, our data suggest there is a need to explore the incorporation of functional parameters in clinical decision making and consider other approaches targeting both right and left ventricular performance to optimise symptomatic outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCPET= cardiopulmonary exercise test\u003c/p\u003e\n\u003cp\u003ePR= pulmonary regurgitation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eVO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003epeak (ml/min) =\u0026nbsp;peak absolute maximum oxygen uptake\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCR= contractile reserve\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eΔFAC=\u0026nbsp;contractile reserve of\u0026nbsp;fractional area change\u003c/p\u003e\n\u003cp\u003eΔLVGLS= contractile reserve of left ventricular global longitudinal strain\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e No external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e The authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval/\u003c/strong\u003e \u003cstrong\u003eConsent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe protocol, informed consent form, participant information sheet and all the study documents were approved by the Health Research Authority (HRA)-Queen Square Research Ethics Committee (Clinical Trial REC Number, 18/LO/0092). All subjects provided written informed consent to participate in the study. IRAS ID is 232328, and the\u0026nbsp;registration date is 16.02.2018.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eGerrah R, Turner ME, Gottlieb D, Quaegebeur JM, Bacha EJPc. Repair of tetralogy of Fallot in children less than 4 kg body weight. Pediatric cardiology ;36(7):1344-9.\u003c/li\u003e\n \u003cli\u003eTernestedt B-M, Wall K, Oddsson H, Riesenfeld T, Groth I, Schollin JJPc. Quality of life 20 and 30 years after surgery in patients operated on for tetralogy of Fallot and for atrial septal defect. 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The international journal of cardiovascular imaging;23(1):25-31.\u003c/li\u003e\n \u003cli\u003eWarnes CA, Williams RG, Bashore TM, Child JS, Connolly HM, Dearani JA, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: a report of the american college of cardiology/american heart association task force on practice guidelines (writing committee to develop guidelines on the management of adults with congenital heart disease) developed in collaboration with the american society of echocardiography, heart rhythm society, international society for adult congenital heart disease, society for cardiovascular angiography and interventions, and society of thoracic surgeons. Journal of the American College of Cardiology;52(23):e143-e263.\u003c/li\u003e\n \u003cli\u003eGeva T, Sandweiss BM, Gauvreau K, Lock JE, Powell AJJJotACoC. Factors associated with impaired clinical status in long-term survivors of tetralogy of Fallot repair evaluated by magnetic resonance imaging. Journal of the American College of Cardiology;43(6):1068-74.\u003c/li\u003e\n \u003cli\u003eM\u0026uuml;ller J, Hager A, Diller G-P, Derrick G, Buys R, Dubowy K-O, et al. Peak oxygen uptake, ventilatory efficiency and QRS-duration predict event free survival in patients late after surgical repair of tetralogy of Fallot. International journal of cardiology;196:158-64.\u003c/li\u003e\n \u003cli\u003eKhoo NS, Young A, Occleshaw C, Cowan B, Zeng IS, Gentles TLJJotASoE. Assessments of right ventricular volume and function using three-dimensional echocardiography in older children and adults with congenital heart disease: comparison with cardiac magnetic resonance imaging. Journal of the American Society of Echocardiography;22(11):1279-88.\u003c/li\u003e\n \u003cli\u003eDavlouros PA, Kilner PJ, Hornung TS, Li W, Francis JM, Moon JC, et al. Right ventricular function in adults with repaired tetralogy of Fallot assessed with cardiovascular magnetic resonance imaging: detrimental role of right ventricular outflow aneurysms or akinesia and adverse right-to-left ventricular interaction. 2002;40(11):2044-52.\u003c/li\u003e\n \u003cli\u003eTzemos N, Harris L, Carasso S, Dos Subira L, Greutmann M, Provost Y, et al. Adverse left ventricular mechanics in adults with repaired tetralogy of Fallot. The American journal of cardiology;103(3):420-5.\u003c/li\u003e\n \u003cli\u003eYazaki K, Takahashi K, Kobayashi M, Yamada M, Iso T, Akimoto S, et al. Exercise echocardiography demonstrates potential myocardial damage in patients with repaired tetralogy of Fallot using layer-specific strain analysis. Cardiology in the Young;30(5):710-6.\u003c/li\u003e\n \u003cli\u003eSteinmetz M, St\u0026uuml;mpfig T, Seehase M, Schuster A, Kowallick J, M\u0026uuml;ller M, et al. Impaired exercise tolerance in repaired tetralogy of fallot is associated with impaired biventricular contractile reserve: an exercise-stress real-time cardiovascular magnetic resonance study. Circulation: Cardiovascular Imaging;14(8):e011823.\u003c/li\u003e\n \u003cli\u003eMeadows J, Powell AJ, Geva T, Dorfman A, Gauvreau K, Rhodes JJTAjoc. Cardiac magnetic resonance imaging correlates of exercise capacity in patients with surgically repaired tetralogy of Fallot. American journal of cardiology;100(9):1446-50.\u003c/li\u003e\n \u003cli\u003eMarx GR, Hicks RW, Allen HD, Goldberg SJJTAjoc. Noninvasive assessment of hemodynamic responses to exercise in pulmonary regurgitation after operations to correct pulmonary outflow obstruction. The American journal of cardiology;61(8):595-601.\u003c/li\u003e\n \u003cli\u003eGiardini A, Specchia S, Coutsoumbas G, Donti A, Formigari R, Fattori R, et al. Impact of pulmonary regurgitation and right ventricular dysfunction on oxygen uptake recovery kinetics in repaired tetralogy of Fallot. European journal of heart failure;8(7):736-43.\u003c/li\u003e\n \u003cli\u003eFreling HG, Willems TP, van Melle JP, van Slooten YJ, Bartelds B, Berger RM, et al. Effect of right ventricular outflow tract obstruction on right ventricular volumes and exercise capacity in patients with repaired tetralogy of fallot. The American journal of cardiology;113(4):719-23.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"peak oxygen consumption, cardiopulmonary exercise testing, echocardiography, pulmonary regurgitation. ","lastPublishedDoi":"10.21203/rs.3.rs-5342548/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5342548/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eReduced exercise capacity in patients with repaired Tetralogy of Fallot cannot be explained wholly by severe pulmonary regurgitation alone. We investigated the effect of pulmonary regurgitation and other measures of left and right ventricular function to identify the principal determinants of exercise performance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003e100 patients with TOF were evaluated, 60 with severe PR and 40 with no or minimal PR. Patients underwent cardiopulmonary exercise testing with concurrent echocardiography. Echocardiography was performed at rest and during exercise (both at low and high intensity for the appropriate parameters). Contractile reserve was expressed as the percentage increase at the relevant time point. Univariate and multivariate linear regression was used to generate a predictive model for exercise function.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThere was no difference in exercise performance between those with and without pulmonary regurgitation when judged by peak absolute oxygen consumption VO\u003csub\u003e2 \u003c/sub\u003e(1695±627vs1744±521, ml/min, p\u0026gt;0.05), or a range of other submaximal cardiopulmonary parameters. Right ventricular volumes were higher in those with pulmonary regurgitation while left ventricular long axis function was reduced. There were no associations between exercise measures with the degree of pulmonary regurgitation and right ventricular volume at rest or during exercise. There was lower contractile reserve of the right ventricle in those with pulmonary regurgitation (fractional area change 20±15 % vs 23±16 %, p\u0026lt;0.05) balanced by improved reserve of the left ventricle. Augmentation of the left ventricular global longitudinal strain and right ventricular fractional area curve together showed the strongest association with peak VO\u003csub\u003e2\u003c/sub\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e There was an overall marked reduction in exercise capacity in patients with repaired tetralogy of Fallot, but no difference between those with and without PR. The degree of exercise limitation is more dependent upon the ability of right and left ventricles.\u003c/p\u003e","manuscriptTitle":"Echocardiographic Determinants of Oxygen Uptake During Exercise in Patients with repaired Tetralogy of Fallot and Severe Pulmonary Regurgitation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-17 08:48:15","doi":"10.21203/rs.3.rs-5342548/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6e6baa90-6af5-4b7c-a566-8ed96349cfa0","owner":[],"postedDate":"December 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-31T06:53:18+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-17 08:48:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5342548","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5342548","identity":"rs-5342548","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}