Association Between Right Atrial Dysfunction and Progression of Right Heart Failure in Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Primary Studies

Introduction: Survival in pulmonary hypertension (PH) is determined by the capacity of the right ventricle (RV) to adapt to a chronically increased afterload, and the right atrium (RA) is the chamber that buffers RV filling during this transition. Phasic RA function can now be quantified with speckle-tracking echocardiography and cardiac magnetic resonance feature tracking (CMR-FT), but individual cohorts are small and use heterogeneous metrics, units and endpoints. We aimed to quantify the association between RA dysfunction and progression of right heart failure in PH, to characterise RA dysfunction relative to healthy controls and to determinants of RV failure, and to evaluate whether RA function is modifiable by afterload-reducing therapy. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. PubMed, Europe PMC, ClinicalTrials.gov and Semantic Scholar were searched from January 2011 to 3 November 2026, complemented by citation searching. Randomised controlled trials (RCTs), comparative studies, cohort studies and case series were eligible. Hazard ratios (HRs) were harmonised to a 1% absolute decrease in RA reservoir strain and pooled with DerSimonian–Laird random-effects models, with Hartung–Knapp–Sidik–Jonkman (HKSJ) intervals and 95% prediction intervals. Mean differences (MD), standardised mean differences (SMD), Fisher-z correlations and pre–post changes were pooled analogously. Risk of bias was assessed with the Quality In Prognosis Studies (QUIPS) tool and the Cochrane RoB 2 tool, and certainty with GRADE. Results: Thirty-five studies (2,843 patients with PH and 408 controls; 2 RCTs, 27 cohort/comparative studies and 6 uncontrolled interventional series) were included, of which 24 contributed to quantitative synthesis. Each 1% absolute decrease in RA reservoir strain was associated with a higher hazard of adverse outcome (HR 1.057 (95% CI 1.032–1.082); 6 studies; 684 patients; I² = 44%; HKSJ 1.021–1.095), corresponding to HR 1.32 (1.17–1.49) per 5% and 1.74 (1.38–2.21) per 10% decrease. The association was consistent for echocardiography and CMR (P for subgroup difference = 0.867) and stronger for composite clinical-worsening/right-heart-failure endpoints (HR 1.091) than for all-cause mortality (HR 1.041; P = 0.037). Impaired conduit (HR 1.136 per 1%) and booster-pump function (HR 1.173 per 1%) were similarly prognostic, and categorical reservoir dysfunction tripled the hazard (HR 3.00 (95% CI 1.49–6.03)). Reservoir strain was lower in PH than in controls (MD −14.1%; SMD −1.44 (95% CI −1.84 to −1.04)) and lower in patients who experienced events (SMD −1.22 (95% CI −1.73 to −0.71)). It correlated with RA pressure (r = −0.44), natriuretic peptides (r = −0.54), RV systolic function (r = 0.66) and RA size (r = −0.45). After afterload-reducing therapy, reservoir strain increased by 4.6% (95% CI 1.2–8.0) and RA area decreased by 3.17 cm² (95% CI −4.37 to −1.97); in a phase 3 RCT, sotatercept reduced mean RA pressure by 2.7 mmHg versus placebo. Discussion: RA dysfunction behaves as a graded, modality-independent marker of RA–RV uncoupling: it is present before RV systolic failure, deepens with RV diastolic stiffness and congestion, predicts clinical worsening and death, and partially recovers when RV afterload is reduced. Most evidence is observational and of moderate risk of bias, and randomised data on RA endpoints remain sparse. Conclusion: RA reservoir strain is independently and dose-dependently associated with progression of right heart failure in PH (moderate certainty), with supportive evidence for conduit and booster dysfunction (low certainty). RA phasic function should be incorporated into multiparametric risk assessment and evaluated as a response marker and secondary endpoint in future RCTs.