Abstract 4147678: Distinct Echocardiographic Signatures Predict Mortality in Scleroderma Pulmonary Vascular Disease

Background: Right ventricular (RV) contractile reserve is a main determinant of outcome in pulmonary arterial hypertension (PAH). PAH and RV maladaptation are common and portend a poor prognosis in the autoimmune disease systemic sclerosis (SSc). Clinical phenotyping of this subgroup of patients, however, remains imprecise. In the present study, we sought to identify whether unique speckle-tracking echocardiography (STE) derived phenotypic signatures predict outcomes in SSc. Methods: In a case-complete study design, 86 SSc patients with technically adequate echocardiograms referred for evaluation of possible PAH, right heart catheterization (RHC), serum laboratories, and pulmonary function testing (PFTs) were included for analysis. RV contractility was assessed using conventional and STE-derived RV free wall strain (RVFWS). Cluster analysis was used to identify sub-groups, which were sub-stratified to adjust for differences in RV afterload as indexed by pulmonary vascular resistance (PVR). A Mann-Whitney test was used for groups comparisons, and Kaplan-Meier survival analysis and Cox regression were used to test association with mortality. Results: Cluster analysis identified two distinct echocardiographic phenotypes in SSc, one with elevated pulmonary pressures (mean PA pressure 44±12 vs. 27±10, p<0.001), markedly elevated PVR (10±6 vs. 4±3 Wood units, p<0.001), and globally reduced RVFWS (-21±6 vs. -13±6 %, p<0.001) compared to the other. This group was associated with increased all-cause mortality (p=0.006). These differences may be driven by the increased PVR in one sub-group vs. another. To test whether RV dysfunction independent of PVR portends poor prognosis, we sub-stratified the cohort into one of three groups ( Figure ), one with relatively lower PVR (<5 WU) and preserved RVFWS, one with lower PVR but reduced RFWS, and one with markedly elevated PVR (>5 WU). This analysis found that patients with low PVR and reduced RVFWS had equally reduced survival (p=0.49) compared with those patients with elevated PVR. Conclusion: Echocardiographic phenotyping utilizing STE-derived RVFWS as a marker of contractile reserve revealed clinically relevant subgroups of RV dysfunction with diminished survival even after adjustment for RV afterload. These findings highlight the utility of STE in identifying SSc patients at greatest risk for poor clinical outcomes.