Prognostic impact of right ventricular–vascular uncoupling in acute heart failure across the left ventricular ejection fraction spectrum: a meta-analysis of multivariable-adjusted data

Background Right ventricular-pulmonary artery coupling (RV-PA) reflects the interaction between ventricular performance and arterial load and is traditionally assessed using pressure-volume loops analysis. In acute heart failure (AHF), direct assessment of RV-PA coupling is rarely feasible due to the practical limitations of manipulating loading conditions in hemodynamically unstable patients. Consequently, non-invasive surrogate measures are used in clinical practice. However, the prognostic significance of non-invasive RV-PA coupling surrogates in AHF across the left ventricular ejection fraction (LVEF) spectrum has not been comprehensively synthesized. Purpose We aimed to perform a systematic review and meta-analysis of multivariable adjusted data to evaluate the prognostic association of RV-PA coupling, measured non-invasively, with all-cause mortality in patients hospitalized with AHF, comparing outcomes across coupling strata. Methods The primary outcome was all-cause mortality. Statistical analysis was performed using Review Manager 7.2.0 (Cochrane Collaboration). Adjusted hazard ratios (aHRs) were pooled using random-effects models with Hartung–Knapp–Sidik–Jonkman adjustment when appropriate. Heterogeneity was assessed with I2 statistics. RV-PA coupling, predominantly assessed using the TAPSE/PASP ratio, was categorized according to study-specific definitions of coupling and uncoupling. Pre-specified subgroup analyses compared AHF with preserved ejection fraction (AHFpEF, LVEF≥50%) versus cohorts spanning the LVEF spectrum. Results Twenty-seven studies (23,043 patients) evaluated RV-PA coupling surrogates; of which 10 studies (9,854 patients) were eligible for quantitative synthesis. RV-PA uncoupling was significantly associated with increased all-cause mortality in AHFpEF-only cohorts (aHR 2.18; 95% CI 1.65–2.88; p = 0.003; I2 = 0%; Figure 1), with no between-study heterogeneity. In contrast, in AHF cohorts spanning the LVEF spectrum, RV-PA uncoupling showed a non-significant trend toward higher all-cause mortality and was characterized by substantial heterogeneity (aHR 1.89; 95% CI 0.89–4.03; p = 0.08; I2 = 75%; Figure 1). Overall, RV–PA uncoupling was associated with a 1.89-fold higher risk of all-cause mortality (aHR 1.89; 95% CI 1.35–2.65; p = 0.002; I2 = 53%), with no significant differences across subgroups. Nonetheless, heterogeneity in coupling definitions limited robust inference. Conclusion In patients hospitalized with AHF, RV-PA uncoupling is associated with higher all-cause mortality, with the most consistent prognostic signal observed in AHFpEF. These findings support the prognostic relevance of RV-PA coupling assessment in AHF and its potential role in refined phenotyping and risk stratification across the LVEF spectrum. Future studies should aim to establish standardized definitions and cut-off values for RV-PA uncoupling.