Association of the Severity of Pulmonary Valve Regurgitation on Biomarkers, Functional Capacity, and Complications in Patients with Heart Failure

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Abstract
Background Pulmonary valve regurgitation (PR) is often encountered in cardiac conditions, including heart failure (HF). Although typically tolerated, severe PR can lead to right ventricular dysfunction and negative clinical outcomes; however, its specific impact within the wider HF population needs further clarification. Objectives This study was designed to evaluate the association between the severity of PR and N-terminal pro-B-type natriuretic peptide (pro-BNP) levels, its effect on functional capacity measured by the six-minute walk test (6MWT), and the incidence of significant clinical problems in patients with HF. Methods Between 2016 and 2023, we conducted a retrospective study involving 579 HF patients who underwent echocardiography at two tertiary institutions. Based on semi-quantitatively evaluated PR severity, patients were classified into four groups: No PR, Mild PR, Moderate PR, and Severe PR. Group comparisons used Chi-square tests and Kruskal-Wallis. Multivariate linear regression and Spearman correlation analyses were performed to assess associations. Results Pro-BNP levels significantly increased across PR severity groups (Median: 2,157 pg/mL [No PR] to 23,541 pg/mL [Severe PR], p<0.0001). In contrast, 6MWT distance significantly decreased with deteriorating PR severity (Median: 254 m [No PR] to 72 m [Severe PR], p<0.0001). The prevalence of orthopnea and pleural effusion also increased with PR severity. After multivariate adjustment, PR severity remained independently associated with higher pro-BNP levels (β=0.48, p=0.002) and lower 6MWT distance (β=-0.39, p=0.008). Conclusion In patients with HF, increasing severity of PR is independently associated with elevated pro-BNP levels, reduced functional capacity, and a higher burden of clinical complications.

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