Abstract
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.
Highlights
Pulmonary arterial hypertension (PAH) is a severe multifactorial disease characterized by increased total pulmonary resistance with subsequent right ventricular (RV) pressure overload [1]
Baseline peak longitudinal strain (PLS) and peak active contraction strain (PACS) were associated with the severity of tricuspid regurgitation
We observed significantly higher PLS and PACS values in patients with mild-to-moderate tricuspid regurgitation compared with patients with severe regurgitation (Supplementary Figure S1)
Summary
Pulmonary arterial hypertension (PAH) is a severe multifactorial disease characterized by increased total pulmonary resistance with subsequent right ventricular (RV) pressure overload [1]. In addition to the right ventricle, remodeling of the right atrium has come into focus in pulmonary hypertension (PH) in the recent years. A loss of that interaction in the sense of RA-RV “uncoupling” results in alterations of RA function to a failing reservoir phase and an impaired conduit component that are inevitably associated with a reduction of cardiac output and RV filling [6]. We aimed to longitudinally assess and characterize RA function in treatment-naïve adult patients with PAH. Right atrial (RA) function has emerged as an important determinant of outcome in pulmonary arterial hypertension (PAH). Studies exploring RA function after initiation of specific pulmonary vascular treatment and its association with outcome in patients with incident PAH are lacking
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