Right ventricular pressure-strain-volume loop-derived myocardial work for the noninvasive assessment of volume overload-induced dysfunction in patients with secondary tricuspid regurgitation
Authors: Fabian A , Szijarto A , Nicoara A , Tokodi M , Tolvaj M , Ujvari A , Ladanyi Z S , Shiida K , Ferencz A , Merkely B , Kovacs A , Lakatos B K 
Published: November 2023

Abstract
Development of secondary tricuspid regurgitation (TR) is associated with poor outcomes in patients with left-sided cardiac diseases. Severe TR imposes substantial volume overload (VO) on the right ventricle (RV), inducing a vicious circle of progressive RV remodelling and dysfunction. Although previous studies have established the value of speckle tracking echocardiography (STE)-derived strain and pressure-strain loop-derived myocardial work indices, these metrics neglect chamber geometry, limiting their utility in conditions accompanied by VO.
Accordingly, we aimed to (1) incorporate instantaneous RV volume into myocardial work calculation to define a method capable of detecting VO-induced RV dysfunction using 3D echocardiography (3DE) and (2) to test its prognostic power in patients with secondary TR.
We enrolled 195 patients (age: 64±15 years, 69% male) with left-sided cardiac diseases and followed them for a median of 42 months. The primary endpoint was all-cause mortality. TR severity was graded according to current guidelines and we compared patients with significant (moderate+) TR (sTR, n=85) versus non-significant TR (nsTR, n=110). All patients underwent 3DE to measure left (LV), and RV volumes and ejection fractions (EF). A reference RV pressure curve was constructed using previously acquired right heart catheterization data and was individually adjusted by non-invasively estimated RV pressures. To obtain RV pressure-strain loops and global myocardial work index (GMWI), RV pressure and 3DE-derived RV circumferential strain tracings were concatenated. We further adjusted GMWI to instantaneous RV volumes (GMWIV) and constructed pressure-strain-volume loops (Figure 1).
Twenty-three patients (11.8%) died during follow-up (16 out of 85 in the sTR group, and 7 out of 110 in the nsTR group). There were no differences in LV and RV volumes and EFs between the sTR and nsTR groups. Interestingly, patients with sTR had significantly higher values of GMWI (sTR vs. nsTR; 667 [438-879] vs. 567 [414-770] mmHg%, p=0.01), whereas GMWIV (292 [169-467] vs. 282 [170-399] mmHg%/mL, p=0.57) did not show difference. We compared patients with versus without adverse outcomes within the sTR group. Patients with sTR who died, presented with significantly lower volume-adjusted GMWIV values (dead vs. alive; 158 [122-332] vs. 312 [207-502] mmHg%/mL, p=0.02), while GMWI did not differ. By Cox regression analysis, GMWIV (hazard ratio [95% CI]: 0.997 [0.994-1.000], p&lt;0.05) was a significant predictor of all-cause mortality in the entire population, whereas GMWI was not.
By integrating RV volume into the pressure-strain relationship, our novel metric could detect the detrimental effects of VO on RV function with prognostic implications in patients with secondary TR. Our approach can be able to capture VO-induced subclinical RV dysfunction that conventional echocardiographic metrics could not unveil.Figure 1