Persistent right ventricular-pulmonary arterial coupling dysfunction and its association with iron metabolism in patients with heart failure

Abstract

In patients with heart failure (HF), a reduced tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio—a surrogate marker for right ventricular-pulmonary arterial (RV-PA) coupling—is a known predictor of poor prognosis (1, 2). This ratio provides integrated information on right ventricular contractility and afterload. While disorders of iron metabolism are recognized as a contributing factor to the progression of HF (3), its specific impact on the long-term persistence of RV-PA coupling dysfunction remains unclear. To identify patients whose TAPSE/PASP ratio remains persistently low after discharge (Persistently Low Group) and to clarify their prognosis and clinical predictors, with a focus on iron metabolism. Of 4,389 patients hospitalized for HF between 2015 and 2023, this study included 595 patients (65% male, mean age 66 ± 16 years) whose TAPSE/PASP ratios were evaluated both during hospitalization and at one-year follow-up. Based on the median in-hospital value of 0.47, patients were classified into two groups: the "Persistently Low Group" (those with a ratio ≤0.47 at both time points) and the "Non-persistently Low Group." Factors associated with persistently low values were analyzed using logistic regression. Prognostic analysis revealed that the Persistently Low Group (n=170) had a significantly higher incidence of the composite endpoint of subsequent HF rehospitalization and all-cause mortality compared to the Non-persistently Low Group (n=425) (log-rank p < 0.05) (Figure). Comparison of clinical backgrounds showed no significant differences in the prevalence of ischemic heart disease or left ventricular ejection fraction. However, in-hospital TAPSE/PASP ratios were significantly lower in the Persistently Low Group than in the Non-persistently Low Group (p < 0.05). Notably, transferrin saturation (TSAT), an indicator of iron deficiency, was significantly lower in the Persistently Low Group than in the Non-persistently Low Group (p < 0.05). Multivariate logistic regression analysis identified low TSAT as a significant independent factor associated with persistent RV-PA coupling dysfunction (odds ratio: 1.03 per 1% decrease; 95% CI: 1.01–1.04; p < 0.05) (Table). HF patients with persistent RV-PA coupling dysfunction after discharge carry an extremely poor prognosis. Low TSAT is a robust, independent marker associated with this treatment-resistant phenotype of RV dysfunction. These findings suggest that TSAT levels may serve as a critical indicator for identifying patients at high risk for persistent RV-PA coupling failure and subsequent adverse outcomes.Kaplan–Meier analysis of prognosisLogistic regression analysis