Dynamic interplay between right ventricular–pulmonary circulation uncoupling and natriuretic peptide release during exercise in heart failure

Background and Aim

Right ventricle–pulmonary circulation (RV–PC) uncoupling is a pivotal marker in the assessment of heart failure (HF) severity and progression, and it independently predicts adverse outcomes, including mortality. N-terminal pro–B-type natriuretic peptide (NT-proBNP) is widely recognized as a reliable biomarker for both the diagnosis and prognostic stratification of HF. The present study sought to evaluate the relationship between NT-proBNP concentrations measured during exercise and the degree of RV–PC uncoupling.

Methods and results

169 consecutive patients referred to a tertiary dyspnea clinic between January 2024 and September 2025 were prospectively enrolled and underwent integrated cardiopulmonary exercise testing with concurrent imaging (CPET imaging). Venous blood samples for NT-proBNP measurement were obtained at baseline (rest), at peak exercise, and during the recovery phase of the maximal CPET imaging protocol.

RV-Pc coupling was evaluated by using the length-force relationship TAPSE/PASP ratio (tricuspid annular plane systolic/excursion pulmonary arterial systolic pressure). Non-parametric comparisons between groups were performed using the Kruskal–Wallis test.

Specifically, NT-proBNP levels were 488,5 [279-1465], 489 [297,5-1595], and 483 [282-1659] in HFpEF, and 453,5 [112-1330], 516 [133-1570], and 523 [133-1610] in HFrEF.

In HF, TAPSE/PAPS at peak exercise decreased compared to rest (0.73 ± 0.19 vs 0.47 ± 0.15 respectively) with an inverse correlation between NT-pro-BNP and TAPSE/PAPS exercise (r=0.69, p<0.01). See figure. Notably, patients exhibiting RV–PC uncoupling at both rest and peak exercise showed higher NT-proBNP levels compared with those demonstrating TAPSE/PASP ratio uncoupling only at peak exercise, as well as with patients with heart failure who maintained a normal TAPSE/PASP ratio at both rest and peak (Figure).

Conclusion

This study identified a concordant relationship between peak TAPSE/PASP ratio and peak NT-proBNP levels. These findings indicate that natriuretic peptide release during exercise may reflect underlying RV–pulmonary circulation uncoupling. Furthermore, they underscore the pivotal contribution of right ventricular dysfunction to biomarker dynamics during maximal exertion in advanced heart failure.NT-proBNP levels across populationsNt-proBNP and TAPSE/PASP at peak in HF