This was a monocentric, single-cohort, observational study. Consecutive patients scheduled for right heart catheterization (RHC) at IRCCS Policlinico San Matteo (Pavia, Italy) from March 2022 to September 2022 were enrolled if in sinus rhythm, with PH of different etiologies, including PH due to advanced left heart failure, and if they had a transthoracic echocardiography performed within two hours of RHC. Exclusion criteria: patients with primary valvular disease or with congenital heart disease. At the end of the observation period, a total of 30 patients were included in the study for analysis. The study complies with the Declaration of Helsinki. Ethical approval for this study is not required as this is a retrospective study. Consent to participate in this study is not required as this is a retrospective study.

Descriptive statistics are reported as mean ± standard deviation for continuous variables, unless skewed, when median and interquartile range are computed, and as count and percentages for categorical variables. Normality was checked by the Shapiro-Wilk test. Comparisons between subgroups were done with the two-sample t-test, Wilcoxon rank-sum (Mann–Whitney) test, and Fisher exact test, when appropriate. Spearman correlation with 95% confidence interval was used to investigate the relationship between invasively derived CI and SVi and the different components of RV GMW.

The study population included 12 male patients and 18 females, mean age was 55 ± 13 years. Etiology was pulmonary arterial hypertension in 19 patients, group 2 PH in 7 patients, group 3 PH in 1 patient, and group 4 PH in 3 patients. The standard RV echocardiographic data and myocardial work parameters are described in Table S1; overall, the patients showed a moderate dilatation of the right ventricle (RV-EDA was 28 cm²) with a preserved systolic function (TAPSE was 20 mm). In 3 out of 30 patients, TR was absent and sPAP and dPAP estimates were not feasible. RHC data are shown in Table S2; overall, patients had a moderate degree of PH (mPAP = 42 mmHg) and a moderately reduced CI (2.3 L/min/m²). Inter-observer variability analysis (Figure S1) showed a mean bias of –0.96% (95% LoA: –2.8%; 4.7%) for RV-GLS with an intra-class correlation coefficient of 0.927 (95% confidence intervals: 0.854–0.965).

As shown in Table 1, GWI, GWE, and GCW were directly correlated with invasively measured SVi and CI, whereas GWW was inversely correlated with SVi and CI. All correlations were of moderate degree, the strongest correlation was between GWI and CI (r = 0.679; p = 0.001). Poorer correlations were observed between TAPSE or TAPSE/sPAP and SVi and CI.

Echocardiographic and hemodynamic characteristics according to the degree of TR are shown in Table 2; patients with moderate/severe TR had slightly, but not significantly, lower CI and SVi values but they had significantly lower TAPSE/sPAP and significantly lower GWE and higher GWW.

Table 3 shows the hemodynamic and echocardiographic values of patients stratified into low-risk vs. intermediate/high-risk categories of RV to PA coupling (TAPSE/sPAP > 0.32 mm/mmHg vs. TAPSE/sPAP ≤ 0.32 mm/mmHg). In both subgroups, those with moderate to severe TR did not differ in terms of CI and SVi but showed significantly lower values of GWE and higher values of GWW (statistical significance was not reached for GWW in the subgroup with preserved RV to PA coupling because of the very small number of patients).

The non-invasive estimation of RV myocardial work via pressure–deformation loops offers a pathophysiologically robust and more comprehensive assessment of RV function compared to conventional echocardiographic indices. RVMW parameters integrate both contractility and pulmonary pressures and are less affected by the presence of TR, which often leads to an overestimation of RV systolic performance with standard measures. Compared to traditional indices, RVMW may thus offer enhanced sensitivity and specificity for detecting subtle alterations in RV function—an important factor for risk stratification and guiding therapeutic decisions in conditions such as advanced heart failure and pulmonary arterial hypertension. In advanced heart failure, for example, grading the severity of RV dysfunction is of outmost importance in patients planned for a left ventricular assist device, to predict whether or not the RV will tolerate the increased flow following implantation; unfortunately, no single echocardiographic parameter can be used to foresee early post-implant RV failure [18]. In patients with pulmonary arterial hypertension, the notion that survival is closely related to RV adaptation to the increased pressure overload has been a consistent finding across studies since more than three decades [19–21]. However, in clinical practice, echocardiographic parameters are not an integral part of any of the risk stratification approaches validated in recent years [22].

This study enrolled only patients in sinus rhythm; therefore, the feasibility and accuracy of RVMW assessment in atrial fibrillation remain unknown. Moreover, while our analysis compared PH patients with significant TR versus those without significant TR, data in patients with isolated significant TR are lacking, and the findings strictly apply to the studied population. It must also be acknowledged that the GMW software was originally designed for left ventricular assessment and required several simplifications to adapt it to the right ventricle. The procedure, however, has been validated against the gold standard [13].

Additionally, the current myocardial work methodology does not account for wall stress, wall thickness, ventricular mass, or wall curvature—factors that are particularly relevant given the complex and irregular geometry of the RV. As a consequence, the calculated myocardial work values for the right ventricle may be less precise than those for the left ventricle. Recent publications investigating the use of 3D speckle tracking echocardiography for RVMW evaluation have shown promising results by potentially overcoming some of the geometric limitations inherent in 2D analyses. However, these 3D approaches remain in the early stages of validation and require further study before they can be routinely applied in clinical practice.

Finally, it is important to note that while the area of the PV loop correlates with myocardial oxygen consumption within the same heart, it does not necessarily permit direct comparisons of oxygen consumption across different hearts. Consequently, our reference to the PV loop area pertains to its utility in estimating myocardial work within each patient rather than drawing direct comparisons between individuals.

RV myocardial work indices can be used in the routine clinical assessment of patients with PH or advanced heart failure. Further studies are required to establish whether this technique may be of clinical value, improving the non-invasive understanding of pathophysiology, prognosis, and response to therapies in all such patients.