Global Longitudinal Strain and Brain Natriuretic Peptide as Prognostic Biomarkers for Asymptomatic Severe Aortic Regurgitation With Preserved Ejection Fraction: Protocol for a Systematic Review and Meta-Analysis

Background: Brain natriuretic peptide (BNP) and global longitudinal strain (GLS) are proposed biomarkers for risk stratification in patients who have asymptomatic severe aortic regurgitation (AR) with preserved left ventricular ejection fraction (EF). While numerous clinical studies have assessed these biomarkers in aortic stenosis, the abstract notes that comparatively few studies have focused specifically on AR. The protocol therefore aims to gather and synthesize available clinical evidence about BNP and GLS as prognostic indicators in this defined patient population without asserting any outcomes.

Methods and scope: This document describes a protocol for a systematic review and meta-analysis following the PRISMA-S extension for literature searches. The planned comprehensive search will include PubMed, Cochrane, and Embase to identify peer‑reviewed, English‑language observational and experimental studies published from database inception through November 2024. Eligible studies are those of adults (age ≥18 years) with severe AR and preserved EF. Study quality will be assessed using the National Heart, Lung, and Blood Institute tool. The abstract reports that search strategy development began in November 2024, a peer review of the search was done in December 2024, and the final strategy was completed in January 2025.

Timeline, analysis, and limitations: According to the protocol timeline provided, database queries and title screening began in January 2025, followed by abstract screening in January–February 2025 and full‑text screening from February–April 2025; data extraction occurred April–May 2025. Synthesis and risk‑of‑bias assessment were planned for April–May 2026, with data analysis in June–July 2026 and manuscript drafting beginning June–July 2026. Manuscript writing and dissemination were scheduled from May–August 2026 with submission to a peer‑reviewed journal by August 2026. The protocol states the review will synthesize existing evidence to determine the prognostic value of BNP and GLS and notes that findings will be based on available published studies and the pre-specified inclusion criteria (English language, publications through November 2024).