Prognostic role of RV PA uncoupling in risk stratification of HFpEF beyond the MAGGIC risk score

Background

Risk stratification in heart failure with preserved ejection fraction (HFpEF) remains suboptimal, as conventional risk scores predominantly reflect left-sided cardiac dysfunction and systemic comorbidities. The MAGGIC Risk Score is widely used for prognostic assessment; however, it does not incorporate parameters of right ventricular–pulmonary vascular interaction, a key determinant of congestion severity and clinical outcomes in HFpEF.

Methods

A total of 389 patients with HFpEF were included (mean age 73 ± 11 years, 60% male, LVEF 55 ± 4%), with a high burden of comorbidities. The MAGGIC Risk Score was calculated for all patients. Optimal cut-off values for the MAGGIC Risk Score and RV–PA uncoupling were derived using receiver operating characteristic (ROC) curve analysis within the study cohort, with RV–PA uncoupling defined as a TAPSE/PASP ratio ≤ 0.34 mm/mmHg. Patients were stratified according to MAGGIC Risk Score alone and MAGGIC combined with RV–PA uncoupling. The primary endpoint was a composite of all-cause mortality and heart failure rehospitalization. Prognostic performance was evaluated using ROC analysis, Kaplan–Meier survival curves, and Cox proportional hazards regression models.

Results

During a median follow-up of 3.5 years, patients with high MAGGIC Risk Score (≥20) and RV–PA uncoupling showed a more advanced clinical phenotype compared with those with high MAGGIC score alone, including a higher prevalence of NYHA III–IV (61% vs 44%, p < 0.001), greater congestion assessed by lung ultrasound B-lines (29 [22–45] vs 20 [8–38], p < 0.001), and increased liver stiffness (20.6 [11–30] vs 8.7 [5.5–19] kPa, p < 0.001). The combined group also exhibited markedly impaired RV–PA interaction (TAPSE/PASP 0.26 [0.22–0.31] vs 0.41 [0.29–0.62] mm/mmHg, p < 0.001) and higher NT-proBNP levels (1841 [1203–4791] vs 1223 [435–2475] pg/mL, p < 0.001).

The MAGGIC Risk Score alone demonstrated limited discrimination for the composite endpoint of death or heart failure rehospitalization (AUC 0.556), whereas incorporation of RV–PA uncoupling significantly improved prognostic performance (AUC 0.697; p = 0.001). Kaplan-Meier analysis showed a significant separation of the survival curves only for the combined model (X 2 :13,44, log-rank p < 0,001) and showed a greater risk of reaching the primary endpoint (HR: 3,18, 95% CI 1,66-6,08, p:0,0005)

Conclusion

In HFpEF, incorporation of RV–PA uncoupling into the MAGGIC Risk Score provides incremental prognostic information and significantly improves risk stratification by identifying a highly congested, high-risk phenotype. This simple echocardiographic marker may enhance clinical risk assessment in routine practice.ROC Curve: MAGGIC + RV–PA UncouplingFor image description, please refer to the figure legend and surrounding text.Kaplan–Meier: MAGGIC + RV–PA UncouplingFor image description, please refer to the figure legend and surrounding text.