This systematic review and meta-analysis showed that RVLS has independent prognostic value for a combined endpoint and all-cause mortality in patients with PH. Collectively, these findings emphasize that RVLS may have value for optimizing current predictive models for clinical events or mortality in patients with PH.

Key points summary 29• Severe aortic valve diseases represent common cardiac abnormalities that are associated 30 with poor long-term survival. 31• Prior to any reduction in left ventricular function, the left ventricle undergoes structural 32 remodeling under the influence of a changing haemodynamic conditions. 33• In this study, we combined temporal changes in LV structure (volume) to alterations in LV 34 functional characteristics (strain, ԑ) into a ԑ-volume loop, to provide novel insight into the 35 haemodynamic cardiac consequences of aortic valve diseases in those with preserved LV 36 ejection fraction. 37• We showed that our novel ԑ-volume loop and the specific loop characteristics provides 38 additional insight in the functional and mechanical haemodynamic consequences of severe 39 aortic valve diseases (with preserved LV ejection fraction). 40• Finally we showed that the ԑ-volume loop characteristics provide discriminative capacity 41 Methods. 27 participants were retrospectively recruited: AR (n=7), AS (n=10) and controls 48 (n=10). Standard transthoracic echocardiography was utilised to obtain apical 4 chamber 49 images to construct ԑ-volume relationships were assessed by: Early systolic ԑ (ԑ_ES), slope of 50 ԑ-volume relation during systole (Sslope), End-systolic peak ԑ (peak ԑ), Diastolic uncoupling 51 (systolic ԑ-diastolic ԑ at same volume) during early diastole (UNCOUP_ED) and late diastole 52 (UNCOUP_LD). ROC-curves were used to determine the ability to detect impaired LV 53 function. 54Results. Whilst LV ejection fraction was comparable between groups, longitudinal peak ԑ was 55 similarly reduced compared to controls. In contrast, ԑ_ES and Sslope were lower in both 56 pathologies compared to controls (P<0.01), but also different between AS and AR (P<0.05). 57 UNCOUP_ED as UNCOUP_LD were significantly higher in both patient groups compared to 58 controls (P<0.05). ROC-curves revealed that loop characteristics (AUC=0.99, 1.00, 1.00; all 59 P<0.01) were better able then peak ԑ (AUC=0. 75, 0.89, 0.76; P=0.06, <0.01 and 0.08, 60 respectively) and LV ejection fraction (AUC=0.56, 0.69, 0.69; all P>0.05) to distinguish AS vs 61 Controls, AR vs Controls and AS vs AR, respectively. 62

Abstract Aims Patients with pre-capillary pulmonary hypertension (PH) show poor survival, often related to right ventricular (RV) dysfunction. In this study, we assessed the 5-year prognostic value of a novel echocardiographic measure that examines RV function through the temporal relation between RV strain (ϵ) and area (i.e. RV ϵ-area loop) for all-cause mortality in PH patients. Methods and results Echocardiographic assessments were performed in 143 PH patients (confirmed by right heart catheterization). Transthoracic echocardiography was utilized to assess RV ϵ-area loop. Using receiver operating characteristic curve-derived cut-off values, we stratified patients in low- vs. high-risk groups for all-cause mortality. Kaplan–Meier survival curves and uni-/multivariable cox-regression models were used to assess RV ϵ-area loop’s prognostic value (independent of established predictors: age, sex, N-terminal pro B-type natriuretic peptide, 6-min walking distance). During follow-up 45 (31%) patients died, who demonstrated lower systolic slope, peak ϵ, and late diastolic slope (all P &lt; 0.05) at baseline. Univariate cox-regression analyses identified early systolic slope, systolic slope, peak ϵ, early diastolic uncoupling, and early/late diastolic slope to predict all-cause mortality (all P &lt; 0.05), whilst peak ϵ possessed independent prognostic value (P &lt; 0.05). High RV loop-score (i.e. based on number of abnormal characteristics) showed poorer survival compared to low RV loop-score (Kaplan–Meier: P &lt; 0.01). RV loop-score improved risk stratification in high-risk patients when added to established predictors. Conclusion Our data demonstrate the potential for RV ϵ-area loops to independently predict all-cause mortality in patients with pre-capillary PH. The non-invasive nature and simplicity of measuring the RV ϵ-area loop, support the potential clinical relevance of (repeated) echocardiography assessment of PH patients.

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Aortic valve replacement (AVR) leads to remodeling of the left ventricle (LV). Adopting a novel technique to examine dynamic LV function, our study explored whether post-AVR changes in dynamic LV function and/or changes in aortic valve characteristics are associated with LV mass regression during follow-up. We retrospectively analyzed 30 participants with severe aortic stenosis who underwent standard transthoracic echocardiographic assessment before AVR [88 (IQR or interquartile range: 22–143) days], post-AVR [13 (6–22) days], and during follow-up [455 (226–907) days]. We assessed standard measures of LV structure, function, and aortic valve characteristics. Novel insight into dynamic LV function was provided through a four-chamber image by examination of the temporal relation between LV longitudinal strain (ε) and volume (ε-volume loops), representing the contribution of LV mechanics to volume change. AVR resulted in immediate changes in structural valve characteristics, alongside a reduced LV longitudinal peak ε and improved coherence between the diastolic and systolic part of the ε-volume loop (all P < 0.05). Follow-up revealed a decrease in LV mass ( P < 0.05) and improvements in LV ejection fraction and LV longitudinal peak ε ( P < 0.05). A significant relationship was present between decline in LV mass during follow-up and post-AVR improvement in coherence of the ε-volume loops ( r = 0.439, P = 0.03), but not with post-AVR changes in aortic valve characteristics or LV function (all P > 0.05). We found that post-AVR improvements in dynamic LV function are related to long-term remodeling of the LV. This highlights the potential importance of assessing dynamic LV function for cardiac adaptations in vivo. NEW & NOTEWORTHY Combining temporal measures of left ventricular longitudinal strain and volume (strain-volume loop) provides novel insights in dynamic cardiac function. In patients with aortic stenosis who underwent aortic valve replacement, postsurgical changes in the strain-volume loop are associated with regression of left ventricular mass during follow-up. This provides novel insight into the relation between postsurgery changes in cardiac hemodynamics and long-term structural remodeling, but also supports the potential utility of the assessment of dynamic cardiac function.