Global Wasted Work Identifies Decompensated Right Heart Failure and Predicts Outcomes in Precapillary Pulmonary Hypertension: A 3D Echocardiographic Study

Global Wasted Work Identifies Decompensated Right Heart Failure and Predicts Outcomes in Precapillary Pulmonary Hypertension: A 3D Echocardiographic Study | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL Echocardiography This is a preprint and has not been peer reviewed. Data may be preliminary. 28 August 2025 V1 Latest version Share on Global Wasted Work Identifies Decompensated Right Heart Failure and Predicts Outcomes in Precapillary Pulmonary Hypertension: A 3D Echocardiographic Study Authors : Ashwin Venkateshvaran [email protected] , Thomas Lindow , Raluca Jumatate , Attila Kovacs , Annika Ingvarsson , Per Lindqvist , and Anna Werther Evaldsson Authors Info & Affiliations https://doi.org/10.22541/au.175637882.26787819/v1 240 views 164 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract AIM. Right ventricular (RV) function plays an important role in determining symptom burden and clinical outcomes in pulmonary hypertension (PH). Global Wasted Work (GWW) quantifies mechanical inefficiencies in RV performance associated with elevated afterload but remains understudied in precapillary PH. We evaluated the relationship between GWW and echocardiographic indices of RV failure, RV remodelling, RV-PA coupling and invasive hemodynamics, and studied its prognostic significance in precapillary PH. METHODS AND RESULTS. Myocardial work indices were assessed using 3D echocardiography in patients with well-defined precapillary PH and simultaneously performed right heart catheterization. Patients with poor image quality, significant valvular lesions and associated left heart disease were excluded. Among 61 patients, those with GWW≥38mmHg/% (n=31) exhibited larger RV end-systolic volume (60 [42 - 71] vs. 42 [35 – 46] ml/m 2 , p=0.009), lower TAPSE (17 [16 – 20] vs. 20 [17 – 23] mm, p = 0.04), higher E a (1.32[0.98 – 1.57] vs. 0.92 [0.64– 1.29] mmHg/ml, p= 0.02) and higher pulmonary vascular resistance (11.1 [8.1 – 14.2] vs. 5.4 [3.4 – 8.7]WU, p=0.002) compared with GWW<38mmHg/%. GWW progressively decreased as RV longitudinal strain and RV-PA coupling improved and increased concomitant to decreasing cardiac index and increasing pulmonary vascular resistance. GWW was associated with increased risk of death or transplantation (HR: 2.5 [1.1 - 5.7]). CONCLUSIONS. Elevated GWW is associated with RV remodelling, worsening RV function and reduced survival in precapillary PH. Further studies are warranted in larger populations to explore potential utility of GWW in risk stratification, treatment monitoring and PH management. Global Wasted Work Identifies Decompensated Right Heart Failure and Predicts Outcomes in Precapillary Pulmonary Hypertension: A 3D Echocardiographic Study Ashwin Venkateshvaran PhD (1,2), Thomas Lindow MD, PhD (3,4), Raluca Jumatate MD (5), Attila Kovacs MD, PhD (6,7), Annika Ingvarsson PhD (8), Per Lindqvist PhD (2), Anna Werther Evaldsson* PhD (8) Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden Department of Diagnostics and Intervention, Clinical Physiology, Umeå University, Umeå, Sweden 1. Department of Medicine, Research and Development, Region Kronoberg, Växjö Central Hospital, Växjö, Sweden 2. Pulmonary Medicine, Allergology, and Palliative Medicine, Department of Clinical Sciences Lund, Lund University 3. Department of Medicine, Central Hospital Kristianstad, Region Skåne, Lund University, Sweden 4. Institute for Clinical Data Management, Semmelweis University, Budapest, Hungary 5. Department of Experimental Cardiology and Surgical Techniques, Semmelweis University, Budapest, Hungary 6. Department of Clinical Sciences Lund, Cardiology, and the Section for Heart Failure and Valvular Disease, Skåne University Hospital, Lund University, Lund, Sweden Running title: Right ventricular myocardial work in pulmonary hypertension Keywords: Pulmonary arterial hypertension, 3D echocardiography, pressure-strain volume loops, Elastance, right ventricular performance, myocardial work Article Type: Original Research Word Count: 4304 words Address for Correspondence: Ashwin Venkateshvaran PhD, FASE, FESC Associate Professor in Clinical Physiology Senior Staff Scientist, Institution for Diagnostics and Intervention Umeå University Sweden Tel: +46 700154786 Email: [email protected] ABSTRACT AIM. Right ventricular (RV) function plays an important role in determining symptom burden and clinical outcomes in pulmonary hypertension (PH). Global Wasted Work (GWW) quantifies mechanical inefficiencies in RV performance associated with elevated afterload but remains understudied in precapillary PH. We evaluated the relationship between GWW and echocardiographic indices of RV failure, RV remodelling, RV-PA coupling and invasive hemodynamics, and studied its prognostic significance in precapillary PH. METHODS AND RESULTS. Myocardial work indices were assessed using 3D echocardiography in patients with well-defined precapillary PH and simultaneously performed right heart catheterization. Patients with poor image quality, significant valvular lesions and associated left heart disease were excluded. Among 61 patients, those with GWW≥38mmHg/% (n=31) exhibited larger RV end-systolic volume (60 [42 - 71] vs. 42 [35 – 46] ml/m 2 , p=0.009), lower TAPSE (17 [16 – 20] vs. 20 [17 – 23] mm, p = 0.04), higher E a (1.32[0.98 – 1.57] vs. 0.92 [0.64– 1.29] mmHg/ml, p= 0.02) and higher pulmonary vascular resistance (11.1 [8.1 – 14.2] vs. 5.4 [3.4 – 8.7]WU, p=0.002) compared with GWW<38mmHg/%. GWW progressively decreased as RV longitudinal strain and RV-PA coupling improved and increased concomitant to decreasing cardiac index and increasing pulmonary vascular resistance. GWW was associated with increased risk of death or transplantation (HR: 2.5 [1.1 - 5.7]). CONCLUSIONS. Elevated GWW is associated with RV remodelling, worsening RV function and reduced survival in precapillary PH. Further studies are warranted in larger populations to explore potential utility of GWW in risk stratification, treatment monitoring and PH management. BACKGROUND Right ventricular (RV) function plays a pivotal role in determining symptom burden and clinical outcomes in pulmonary hypertension (PH). 1 Adaptability of the right ventricle to increased afterload due to elevated peripheral vascular resistance directly impacts exercise capacity, disease progression and survival. 2 During early stages of adaptation, RV contractility increases to preserve RV-pulmonary arterial (PA) coupling and sustain forward stroke volume through the pulmonary circuit. As afterload increases, this adaptation fails, resulting in RV–PA uncoupling, RV dilation, and eventual decompensation. Early recognition of RV decompensation is essential, as timely intervention may improve patient outcomes. The reference diagnostic to assess RV-PA coupling is pressure-volume loop derived ration of RV end-systolic elastance to arterial elastance (E es /E a ) ratio. However, invasive assessment is impractical in routine practice. Echocardiographic surrogates of E es and E a offer non-invasive alternatives to assess RV-PA coupling in clinical practice, 3 4 and may overcome limitations of conventional indices, which are strongly load-dependent. 5 Advances in 3D echocardiography permit integration of strain imaging with pressure estimates to to derive myocardial indices, providing load-adjusted insights into RV performance. 6 Global myocardial work index (GWI), global myocardial constructive (GCW) and global wasted work (GWW) have shown stronger association with invasive pulmonary vascular resistance than conventional echocardiographic measures. 7 Reduced GCW and GWI have also shown associations with all-cause mortality in precapillary PH. 7 In contrast, GWW, reflecting inefficient energetics due to paradoxical lengthening during ejection and shortening during isovolumic relaxation, remains understudied. Given that RV-PA uncoupling is a hallmark of progressive PH, assessment of GWW may provide novel insights into RV decompensation and disease progression. We therefore aimed to evaluate the relationship between GWW and echocardiographic markers of RV remodeling and RV-PA coupling, and to determine its prognostic value in precapillary PH. METHODS Study Population. We screened patients enrolled prospectively with PAH or chronic thromboembolic PH (CTPH) referred for right heart catheterization (RHC) at two tertiary PAH centers in Sweden (Skane University Hospital, Lund and Norrlands University Hospital, Umeå) between 2012 and 2024. Pre-capillary PH was defined by RHC as pulmonary artery mean pressure (PAMP) ≥ 20 mmHg or 25 mmHg, pulmonary artery wedge pressure (PAWP) 2 or 3 Wood Units (WU) consistent with diagnostic criteria at the time of enrollment. 8 9 We included patients > 18 years with a maximum interval of 1 day between RHC and echocardiography. Patients with atrial fibrillation or significant arrhythmias, pacemakers, poor echocardiographic images, more than moderate valve regurgitation or stenosis and patients who had undergone sternotomies during open-heart surgery were excluded. The study was approved by the Regional Ethical Review Board of Lund (EPN-Dr-2010-114, 2010-442 and 2023-06923-0) and Umeå (Dnr 07−092 M) and complies with the Declaration of Helsinki. All participants provided written, informed consent. Echocardiography. All patients underwent standard, comprehensive echocardiograms in keeping with current guidelines 10 employing commercial ultrasound systems (Vivid E9, General Electric, Horten, Norway; Philips iE33 or EPIQ CVx, Eindhoven, Netherlands) equipped with an adult matrix-array transducer. 2D gray-scale images were acquired at 50-80 frames/sec and Doppler tracings were recorded using a sweep speed of 75-100mm/sec. Studies were performed at both centers under expert supervision (P.L in Umeå, AWE in Lund) employing a standard acquisition protocol. Pharmacological status was unaltered between echocardiography and RHC. 2D and Doppler digital loops were stored and analyzed offline (EchoPAC PC, version 11.0.0.0 GE Ultrasound, Waukesha, Wisconsin or Philips Intellispace Cardiovascular, version 8.0, Eindhoven, Netherlands). Left ventricular diameter (LVIDd), interventricular septal thickness (IVSd), and posterior wall thickness (PWd) were measured in diastole in the parasternal long-axis view. LV ejection fraction (EF) was measured in the apical 4- and 2-chamber views using Simpsons biplane method. RV dimension (RVIDd) and tricuspid annular plane systolic excursion (TAPSE) were measured in the RV-focused apical view. RV systolic pressure (RVSP) was estimated from peak systolic tricuspid regurgitation in addition to estimated right atrial pressure obtained from inferior vena cava size and collapse. 11 Three-dimensional echocardiography datasets were exported and analyzed using a dedicated 4D RV-Function software (Ultrasound Workspace, TomTec Imaging GmbH, Unterschleissheim, Germany). While assessing the 3D datasets, special care was given to delineate the whole cavity of the RV, including the outflow tract, and manual correction was performed when deemed necessary. RV end-diastolic (RVEDV) and end-systolic volumes (RVESV), stroke volume (RVSV) and ejection fraction (RVEF) were assessed in accordance with current recommendations. 12 RV contractility (E es ) was assessed as the ratio between RV end-systolic pressure (RVSP x 0.9) by Doppler and RVESV obtained by 3D echocardiography using the previously validated single-beat method. 13 Arterial elastance (E a ) was assessed as the ratio between RV end-systolic pressure and RVSV. E es /E a was subsequently calculated as the ratio between E es and E a . Additionally, TAPSE/RVSP was assessed as a surrogate of E es /E a and was employed as an indirect assessment of the ventricular length-tension relationship. 3 In this context, TAPSE serves as an estimate of longitudinal systolic function, while RVSP represents afterload. Non-invasive Pressure-Strain loops and Myocardial Work Indices. Reconstructed 3D mesh models were imported into the ReVISION software https://revisionmethod.com/ (Argus Cognitive, Inc., Hanover, NH, USA), employing a previously reported and validated methodology. 6 14 3D-derived RV global circumferential and longitudinal strain, global myocardial work index (GWI), global constructive work (GCW) and global wasted work (GWW) were assessed. A non-invasive RV pressure curve was reconstructed using the peak systolic RV pressure value as previously described. 14 Briefly, the peak systolic RV pressure was employed as a single input for a validated multilayer perceptron model that reconstructed a pressure curve considering all valvular events and the entire cardiac cycle. This approach has been validated against invasive reference-standard pressure–volume analysis in earlier studies. 6 Pressure–strain relationship-derived myocardial work was characterized by the following metrics; GWI, the area under the pressure-strain loop represents total myocardial work during the cardiac cycle, GCW represents the sum of myocardial work contributing to effective contraction (shortening during systole and lengthening during isovolumic relaxation), and GWW represents ineffective myocardial contraction (lengthening during systole and shortening during isovolumic relaxation). Finally, global myocardial work efficiency (GWE) was calculated as GCW/GCW+GWW, global area myocardial work as GWIarea/RVEDV and global circumferential myocardial work as GWIc/RVEDV. Right Heart Catheterization. RHC was performed using a 6F Swan Ganz catheter (Edwards Lifesciences) employing jugular or femoral access. Mean right atrial pressure (mRAP), pulmonary artery systolic- (sPAP), mean- (mPAP), and pulmonary artery wedge pressure (PAWP) were obtained under fluoroscopic guidance after calibration with the zero-level set at the mid-thoracic line. A dedicated gas analysis system measured breath-to-breath oxygen consumption. Cardiac Output (CO) was estimated using the Thermodilution principle. Pulmonary vascular resistance (PVR) was estimated as PAMP/CO. All pressure tracings were stored (WITT Series III, Witt Biomedical Corp., Melbourne, FL) and analyzed offline. Inter- and intraobserver variability. To evaluate the intra- and inter-observer variability GWW was measured in 5 subjects by the same investigator (PL), and by two different investigators (AWE, AI). Statistical Analysis. Continuous variables were expressed as median and interquartile range after normality was visually dismissed using QQ plots. Categorical variables were expressed as numbers and proportions in percentages. Patient subgroups were compared using the Mann–Whitney U test. GWW distribution across tertiles was compared using the Kruskal-Wallis Test. Correlations between myocardial work and RHC parameters were assessed using Spearman’s Rank Correlation. Intraclass correlation coefficient (ICC) and Bland-Altman plots were used to assess intra- and inter-observer variability. 15 ICC was predefined as poor (<0.5), adequate (0.5 – 0.74), good (0.75 – 0.89), or excellent (≥0.90). Time-to-event analysis was performed using Kaplan–Meier curves, and the association between GWW and the composite outcome of death or lung transplantation was assessed with Cox proportional hazards regression, both unadjusted and adjusted for age and sex. Results are presented as hazard ratios (HR) with 95% confidence intervals (CI). Model discrimination was evaluated using C-statistics. The proportional hazards assumption was assessed using Schoenfeld residuals and was not statistically violated. Linearity of the continuous GWW variable was evaluated with Martingale residuals, which indicated a non-linear relationship; therefore, GWW was modelled as a categorical variable using a median cutoff of 38 mmHg/%. A possible time-varying effect of GWW was assessed by including an interaction term between GWW and time. Cox models with and without the interaction term were compared using the likelihood ratio test. Tests were performed at 95% confidence intervals and a p-value < 0.05 was considered statistically significant. IBM SPSS statistics version 23.0 and R version 4.2.1 (R Core Team, Vienna, Austria) were employed for statistical analysis. RESULTS Of a total of 139 PH patients evaluated at both centers, 65 (46%) were excluded owing to inadequate image quality for 3D analysis, 4 (3%) owing to severe concomitant valve disease, 1 (0.7%) owing to absence of tricuspid regurgitation and 6 (4%) owing to left heart disease. In effect, 61 patients with precapillary PH were included in this study. Patients were predominantly women (n = 45, 74%) and presented largely with NYHA class II (48%) or III (36%) symptoms, deranged pulmonary hemodynamics and reduced functional capacity (Table 1) . Eighty-five percent of the population had pulmonary arterial hypertension (PAH), while a minority was diagnosed with chronic thromboembolic PH (CTEPH). Myocardial Work and RV-PA coupling. Two-dimensional, Doppler, 3D echocardiographic data, RV myocardial work indices, RV-PA coupling and RHC data of the patient population are presented in Table 2 , stratified by median GWW. In the total population, the right heart was dilated and exhibited decreased RV performance indices. Precapillary PH patients with GWW ≥ 38mmHg/% (High GWW) displayed larger RV end-systolic volume, lower TAPSE, RV longitudinal and circumferential strain, and higher PASP when compared with GWW <38 mmHg/% (low GWW) The High GWW group also showed evidence of RV-PA uncoupling, as indicated by higher E a , lower RV E es /E a (0.47 [0.34 – 0.73] vs. 0.71 [0.50 – 0.91]; p = 0.007) and TAPSE/PASP ratio (0.21 [0.18 – 0.32] vs 0.34 [0.22– 0.45 ] mm/Hg; p = 0.003). On RHC, the High GWW group displayed higher PAMP and PVR than Low GWW (Table 2). We also performed supplementary analysis comparing myocardial work indices between PAH and CTEPH. No significant differences were found between groups (Supplemental Table 1). Looking specifically at hemodynamic markers of RV decompensation, we compared GWW between patients having normal (<8mmHg) and elevated RAP (≥8mmHg) by RHC, in addition to preserved (≥2.2L/m 2 ) and reduced cardiac index (<2.2L/m 2 ). GWW was significantly higher in the subgroup with reduced cardiac index (56 [33 -94] vs. 31 [19 – 40] mmHg/%, p = 0.005), but did not differ between patients with elevated and normal RAP (46 [29 -85] vs. 38 [20 -59] mmHg/%, p = 0.31). RV strain-volume loops in a patient with decompensated and non-decompensated RV function are illustrated in Figure 1. RV remodeling and association with invasive hemodynamics. To study trends with RV maladaptation and worsening RV-PA coupling, we compared GWW across tertiles of variables representing RV size (indexed RVEDV), function (RV longitudinal strain), RV-PA coupling (E es /E a ratio), in addition to hemodynamic variables RAP, CI and PVR (Figure 2). GWW was significantly higher between RVEDV tertile 1 and 3, suggesting higher wasted work with larger RV volumes. Further, GWW progressively decreased across RV longitudinal strain and Ees/Ea tertiles suggesting lower wasted work, enhanced myocardial deformation and more optimal RV-PA coupling. On catheterization, GWW progressively increased across PVR tertiles and decreased across CI tertiles. RV myocardial work measures displayed a modest association with catheterization-derived hemodynamics. GWW displayed weak to moderate correlations with PAMP and PVR. GWI and GCW demonstrated a weak positive correlation with PAWP. GWE, GWWI, GWVIc and GWIVarea displayed modest positive correlations with PVR (Table 3). Prognostic Value in Precapillary PH. During a median follow-up period of 47 months (IQR: 33–61), overall survival was 78.6% at 2 years and 25% at 5 years. Twenty-six patients (43 %) died, and 4 patients (7 %) underwent a lung transplantation. Kaplan-Meier survival curves stratified by median GWW are presented in Figure 3. GWW ≥ 38mmHg/% was associated with higher risk of death or lung transplantation (unadjusted HR: 2.4 [1.1 - 5.5], C statistic: 0.61 [0.50 - 0.71]), HR adjusted for age and sex: HR: 2.5 [1.1 - 5.7]. The effect of higher GWW was found to change significantly over time (p for interaction with time < 0.001), suggesting that this estimate represents an average HR, and that the true relative risk possibly increases with time. Intra- and interobserver agreement GWW demonstrated good inter- (ICC = 0.80; Bias = − 17 ± 61mmHg%) and intraobserver agreement (ICC = 0.85; Bias = − 14 ± 58mmHg) suggesting high measurement reproducibility. DISCUSSION In this study, elevated GWW was associated with adverse RV remodeling characterized by larger RV volumes, reduced RV performance and impaired RV-PA coupling indices. GWW displayed significant association with invasive hemodynamic indices of afterload, including PAMP and PVR. Finally, patients with elevated GWW demonstrated worse long-term survival, suggesting a potential role for prognostic evaluation in precapillary PH. Although the relatively small cohort and modest feasibility limits generalizability of our findings, GWW shows promise as a novel, non-invasive diagnostic and prognostic marker in PH. Myocardial work in precapillary PH. Precapillary PH patients exhibited elevated GWW, GCW, GWI and GWE consistent with previous studies examining the impact of increased afterload on RV function. 7 16 When compared with HF patients with secondary PH, earlier studies show that precapillary PH displays higher GWW but lower GWI, GWE and GCW. 7 Elevated PVR in PAH leads to increased myocardial energy expenditure that does not primarily contribute to ejection, explaining the increased GWW. Reduced productive myocardial work as seen in lowered GCW has been described in other studies offering a mechanistic explanation for impaired systolic function in PAH owing to underfilling. 17 The difference in relationship between GWW and other work indices may have to do with primary myocardial disease in HF and suggests a role for the interrelationship between GWW and other myocardial work indices to distinguish primary PAH (Group 1) from PH secondary to left-sided HF (Group 2). This needs to be evaluated in further studies. The generally lower GWW values observed in our study compared to previously reported data may, in part, reflect methodological differences. Specifically, we utilized a dedicated software based on 3D RV datasets to calculate GWW, whereas earlier studies primarily employed 2D approaches originally designed for the LV. 7 16 Previous studies comparing 2D and 3D echocardiographic approaches for assessing right ventricular size and function have demonstrated significant discrepancies, with 2D methods tending to underestimate both dimensions and volumes. 18 It is plausible that the divergencies in approach also impact myocardial work indices. However, this will need to be further studied. Additionally, comparison between patient cohorts in our study and previous data suggest no significant differences in age or PAMP between cohorts. However, PVR was significantly higher in our cohort (8.7 vs 6.2 WU), which may have influenced myocardial work indices that incorporate afterload elevation. RV Remodelling and Invasive Associations. To the best of our knowledge, this is the first study to suggest that GWW is associated with an increase in RVEDV, reduction in RV systolic function and RV-PA uncoupling. Previous studies using cardiac MRI have established a normal E es /E a ratio range of 1.5-2.0, with RV failure onset occurring when E es /E a drops below a critical threshold of 0.8. 4 In addition to suggesting an association between GWW and E es /E a , our data indicates a lower optimal cut-off for echocardiographic SV/ESV as an E es /E a surrogate to identify RV decompensation. This discrepancy may be attributable to different imaging modalities employed to establish these thresholds. The modest correlation between RV myocardial work indices and invasive PVR compared with earlier studies 7 may be due to measurement variability, study design and small sample size that may not have captured the full range of hemodynamic variations. Prognosis. A previous study in PH reported that reduced GCW and GWI were associated with worse prognosis, whereas GWW did not emerge as a significant predictor of all-cause mortality. 7 In contrast, our findings suggest a more prominent role for GWW in prognostication. It is plausible that GWW accounts for both myocardial work and energetic inefficiency due to afterload mismatch, while GCW and GWI primarily focus on ventricular performance and may not capture ventricular inefficiencies secondary to RV-PA uncoupling. These differences may also reflect variations in patient population, disease severity and methodological approaches. Importantly, the small sample size in our study warrants caution in the interpretation and generalization of these findings. Large, multi-center studies are necessary to validate our findings and more precisely define the prognostic utility of GWW in precapillary PH. Clinical Implications. Based on our findings, GWW shows promise as a novel adjunctive marker for identifying RV decompensation and maladaptive remodeling in precapillary PH. Further, serial investigations may be useful to monitor disease progression and for evaluation of treatment response. Current models for risk stratification in PH largely rely on functional capacity assessment and invasive hemodynamics. Integration of GWW into risk assessment may improve early detection of high-risk patients who may benefit from early therapeutic interventions. Further studies are necessary to investigate whether GWW can be utilized as a non-invasive marker for therapy regulation during pharmaceutical treatments and to assess favorable responses to new therapies. Study Strengths and Limitations. The strengths of this study include a novel, systematic evaluation of myocardial work indices in precapillary PH employing comprehensive echocardiography, an RV dedicated software and invasive hemodynamics. Study limitations include a small sample size that limits the generalizability of our results and, hence, warrant external validation. A large proportion of patients needed to be excluded from analysis owing to inadequate image quality for 3D analysis. This isn’t uncommon in PAH, where right heart dilatation and pressure-overload often hinder acquisition of complete and high-quality 3D volume datasets. The patients were also in different stages of disease presentation, and further studies focused on treatment-naïve PAH patients could be of interest for prognostication. Subgroup analysis was further limited by the predominance of PAH over CTEPH. Further, longitudinal analysis was not performed so changes in GWW over time could not be assessed. Schoenfeld’s residuals did not indicate any violation of the assumption of proportional hazards. Nonetheless, an interaction with time was found, possibly explained by the small sample size. Also, the small sample size did not allow for complete adjustment of potential confounders and residual confounding beyond age and sex is likely present. This emphasizes the limitations of the small sample size and the results regarding the prognostic value for GWW needs to be interpreted cautiously, and preferably reproduced in future, larger studies. Conclusion. Elevated GWW is associated with adverse RV remodelling and worse survival in precapillary PH. GWW shows potential as a non-invasive marker for risk stratification and treatment monitoring. Future prospective, multicentre studies are warranted to evaluate the clinical utility of GWW in PH management. Acknowledgements None Conflicts of Interest None to Declare Funding sources None Relevant disclosures The authors used an AI-based language tool (ChatGPT, OpenAI) to assist with grammar and style editing during manuscript preparation. The tool was not used for data analysis, interpretation, or generation of scientific content. 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Collection Echocardiography Keywords 3d echocardiography elastance myocardial work pressure-strain volume loops right ventricular performance Authors Affiliations Ashwin Venkateshvaran [email protected] Skanes universitetssjukhus Lund View all articles by this author Thomas Lindow Centrallasarettet Vaxjo View all articles by this author Raluca Jumatate Centralsjukhuset Kristianstad View all articles by this author Attila Kovacs Semmelweis Egyetem Klinikai Kozpont View all articles by this author Annika Ingvarsson Skanes universitetssjukhus Lund View all articles by this author Per Lindqvist Umea Universitet Institutionen for diagnostik och intervention View all articles by this author Anna Werther Evaldsson Skanes universitetssjukhus Lund View all articles by this author Metrics & Citations Metrics Article Usage 240 views 164 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Ashwin Venkateshvaran, Thomas Lindow, Raluca Jumatate, et al. Global Wasted Work Identifies Decompensated Right Heart Failure and Predicts Outcomes in Precapillary Pulmonary Hypertension: A 3D Echocardiographic Study. Authorea . 28 August 2025. DOI: https://doi.org/10.22541/au.175637882.26787819/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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