Clinical Relevance of Right Atrial Functional Response to Treatment in Pulmonary Arterial Hypertension.

Background: Right atrial (RA) function has emerged as an important determinant of outcome in pulmonary arterial hypertension (PAH). However, studies exploring RA function after initiation of specific pulmonary vascular treatment and its association with outcome in patients with incident PAH are lacking. Methods: RA peak longitudinal strain (PLS), passive strain (PS), and peak active contraction strain (PACS) were retrospectively assessed in 56 treatment-naïve patients with PAH at baseline and during follow-up after initiation of specific monotherapy or combination therapy. Patients were grouped according to their individual RA functional response to treatment, based on change from baseline (Δ): worsened (first Δ-tertile), stable (second Δ-tertile), and improved (third Δ-tertile). The Spearman's rho correlation and linear regression analysis were used to determine associations. Time to clinical worsening (defined as deterioration of functional class or 6-min walking distance, disease-related hospital admission, or death) was measured from the follow-up assessment. The association of RA functional treatment response with time to clinical worsening was assessed using the Kaplan-Meier and the Cox regression analyses. Results: Median (interquartile range) time to echocardiographic follow-up was 11 (9-12) months. Of the 56 patients, 37 patients (66%) received specific dual or triple combination therapy. Δ RA PLS during follow-up was significantly associated with changes in key hemodynamic and echocardiographic parameters. The change of pulmonary vascular resistance, right ventricular (RV) end-systolic area, and global longitudinal strain were independently associated with Δ RA PLS. The median time to clinical worsening after echocardiographic follow-up was 6 (2-14) months [17 events (30%)]. In the multivariate Cox regression analysis, worsening of RA PLS was significantly associated with clinical deterioration (hazard ratio: 4.87; 95% CI: 1.26-18.76; p = 0.022). Patients with worsened RA PLS had a significantly poorer prognosis than those with stable or improved RA PLS (log-rank p = 0.012). By contrast, PS and PACS did not yield significant prognostic information. Conclusion: Treatment-naïve patients with PAH may show different RA functional response patterns to PAH therapy. These functional patterns are significantly associated with clinically relevant outcome measures. Improvements of RA function are driven by reductions of afterload, RV remodeling, and RV dysfunction.
Competing Interests: MR has received support from Bayer; speaker fees from Bayer, Janssen-Cilag GmbH, and OMT and consultancy fees from Bayer and Janssen-Cilag GmbH. PD reports personal fees and non-financial support from Actelion, non-financial support from Astra Zeneca, non-financial support from Bayer, non-financial support from GSK, personal fees and non-financial support from MSD, non-financial support from Novartis, non-financial support from Teva, non-financial support from Boehringer Ingelheim, non-financial support from Vifor, non-financial support from Menarini outside the submitted work. HG has received consultancy fees from Bayer, Actelion, Pfizer, Merck, GSK, and Novartis; fees for participation in advisory boards from Bayer, Pfizer, GSK, Actelion, and Takeda; lecture fees from Bayer HealthCare, GSK, Actelion, and Encysive/Pfizer; industry-sponsored grants from Bayer HealthCare, Aires, Encysive/Pfizer, and Novartis; and sponsored grants from the German Research Foundation, Excellence Cluster Cardiopulmonary Research, and the German Ministry for Education and Research. WS has received speaker/consultancy fees from Abivax, Bayer AG, Liquidia Technologies, Pieris Pharmaceuticals, United Therapeutics and Vectura. HG has received fees from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. KT has received speaking fees from Actelion and Bayer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Richter, Zedler, Berliner, Douschan, Gall, Ghofrani, Kimmig, Kremer, Olsson, Brita da Rocha, Rosenkranz, Seeger, Yogeswaran, Rako and Tello.)